Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate B cell responses and also infiltrate ...

BACKGROUND: Chronic hepatitis C virus infection is a leading cause of cirrhosis and hepatocellular carcinoma. Both advanced solid tumors and hepatitis C have previously been associated with memory B-cell dysfunction. In this study we sought to dissect the impact of viral infection, cirrhosis and liver cancer on memory B-cell frequency and function in the ...

Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive extracellular matrix (ECM) deposition in the skin and other visceral organs and it is associated with immune activation characterized by autoantibody production, release of various cytokines and T-lymphocyte activation. Several recent lines of evidence in animal models and in SSc patients indicate a ...

Chronic hepatitis C virus (HCV) infection is associated with cirrhosis, autoimmunity and lymphoproliferative disorders. We have previously reported a differential regulation of T and B lymphocytes by HCV core protein in vitro. In this report, we employed a translational approach to characterize the activation status of peripheral B cells from individuals ...

Systemic lupus erythematosus (SLE) is an autoimmune disease caused by abnormal immune regulation and excessive production of autoantibodies, which characterized by T and B cell dysfunction and excessive production of pathological cytokines and autoantibodies. Vascular endothelia and subendothelial collagen were ...

Kawasaki disease is an acute febrile disease causing vasculitis, which may lead to as severe a complication as myocardial infarction. This disease is characterized by marked activation of the immune system, including elevation of various cytokines, polyclonal B cell activation, and decrease of CD8+ cells. The high levels of ...

Apart from its role in the synthesis of protein and nitric oxide (NO), and in ammonia detoxification, the amino acid arginine exerts an immunosupportive function. We have studied the role of arginine in immune defense mechanisms in the developing postnatal immune system. In suckling mice, arginine is produced in the small intestine. In F/A-2^+/+ transgenic mice, which ...

B cells play an important role in the pathogenesis of both systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce autoantibodies, but are also specialized to present specific autoantigens efficiently to T cells. Furthermore, these B cells can ...

The activation of transcription factor NF-?B is controlled by two main pathways: the classical canonical (RelA/p65-p50)- and the alternative noncanonical (RelB/p52)�NF-?B pathways. RelB has been shown to play a protective role in RelA/p65-mediated proinflammatory cytokine release in immune�inflammatory lymphoid cells. Increased infiltration of macrophages and lymphoid ...

Inflammatory mediators, including cytokines, contribute to neuronal and axonal dysfunction and cell death. To examine the roles of cytokines in pathogenesis and regeneration in the central nervous system (CNS), we analyzed effects of cytokines on early gene regulation (6h) in neuronal cultures, employing gene arrays. Our hypothesis is ...

B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia. Deregulation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene in mouse B cells causes a CD5-positive leukemia similar to aggressive human B-CLLs. We recently reported that levels of TCL1 expression in B-CLL are regulated by miR-29 and miR-181 that target 3' ...

Aims/hypothesisUnderstanding cellular and molecular events in diabetes mellitus will identify new approaches for therapy. Immune system cells are important modulators of chronic inflammation in diabetes mellitus, but the role of B cells is not adequately studied. The aim of this work was to define the function of B ...

HCV infection is associated with immune dysregulation and B cell Non-Hodgkins lymphoma (HCV-NHL). We have previously shown in vitro that HCV core protein differentially regulates T and B cell functions through two negative signaling pathways, programmed death-1 (PD-1) and suppressor of cytokine ...

An adult patient with acute lymphoblastic leukemia associated with a 14q+ marker chromosome is presented. The abnormally resulted from a translocation of material from the long arm of chromosome 11. The leukemic cells were found to be B cells on the basis of surface immunoglobulins, lack of receptors for sheep erythrocytes, and a ...

IL-17 is a cytokine with powerful proinflammatory activity. Production of IL-17 is abnormally increased in patients with systemic lupus erythematosus (SLE), a multiorgan chronic autoimmune disease. In patients with SLE, CD3⁺CD4^?CD8^? (double negative) T cells are an important source of ...

Feb 12, 2008... B cells, NK cells, monocyte/ macrophages/dendritic cells, hematopoietic stem cells and cytokine networks can be negatively affected. ...

Casitas B-cell lymphoma (Cbl)-family E3 ubiquitin ligases are negative regulators of tyrosine kinase signaling. Recent work has revealed a critical role of Cbl in the maintenance of hematopoietic stem cell (HSC) homeostasis, and mutations in CBL have been identified in myeloid malignancies. Here we show that, in contrast to Cbl or Cbl-b single-deficient mice, concurrent loss ...

B lymphocytes play roles in many autoimmune diseases characterized by unresolved inflammation, and B cell ablation is proving to be a relatively safe, effective treatment for such diseases. B cells function, in part, as important sources of regulatory cytokines in autoimmune disease, but ...

Breach of B cell tolerance is central to the pathogenesis of systemic lupus erythematosus (SLE). However, how B cell tolerance is subverted in human SLE is poorly understood due to difficulties in identifying relevant autoreactive B cells and in obtaining lymphoid tissue. ...

In germinal centers (GCs), B cells are selected through interaction with follicular dendritic cells bearing immune complexes and follicular helper T (Tfh) cells secreting Tfh cytokines, including IL-21. To analyze these cellular interactions, we have explored culture conditions that can simulate GC B ...

Atopic dermatitis (AD) is a common allergic disease and constitutes a huge social and economic burden for the whole country. AD usually heralds other allergic diseases, such as asthma and allergic rhinitis. The pathogenesis of AD remains to be studied but generally includes abnormal skin barrier and aberrant cutaneous immune responses. Biomarkers are important in monitoring ...

B cells play a variety of immunoregulatory roles through their antigen-presentation ability and through cytokine and chemokine production. Innate immune activation of B cells may play a beneficial role through the generation of natural cross-reactive antibodies, by maintaining ...

, centroblasts (CBs) and memory B cells,3 could also capture the substructure that we had identified in primary the miRNA signature of the MG-B subgroup was closely related to that of memory B cells, a significant cells mechanistically define the microRNAprofile of diffuse large B-cell lymphoma ...

BackgroundChildren born to HIV+ mothers are exposed intra-utero to several drugs and cytokines that can modify the developing immune system, and influence the newborn's immune response to infections and vaccines. We analyzed the relation between the distribution of cord blood lymphocyte subsets and cytokine profile in term newborns of HIV+ mothers using ...

B cell development requires the coordinated action of transcription factors and cytokines, in particular interleukin-7 (IL-7). We report that mice lacking the POZ (Poxvirus and zinc finger) domain of the transcription factor Miz-1 (Zbtb17(?POZ/?POZ)) almost entirely lacked follicular B cells, ...

B cells are generally considered to positively regulate immune responses by producing antigen-specific antibodies. B cells are classified into classical CD5(-) conventional B cells and CD5(+) B1 cells. The latter produce multi-specific autoantibodies and are thought to be ...

B cells are generally considered to positively regulate immune responses by producing antigen-specific antibodies. B cells are classified into classical CD5^- conventional B cells and CD5⁺ B1 cells. The latter produce ...

B cells respond to a variety of effector molecules that can induce these cells to differentiate. One such molecule is the neuropeptide, substance P (SP). Previous studies have demonstrated the presence of SP receptors on lymphocytes while limited studies have been able to demonstrate the biological significance of their expression. SP has been shown to ...

The adaptor protein Shc is phosphorylated downstream of many cell surface receptors, including antigen and cytokine receptors. However, the role of Shc in B cell development has not been addressed. Here, through conditional expression of a dominant negative Shc mutant and conditional loss of Shc protein expression, we tested a role for ...

Classical BCR signaling requires a number of signalosome mediators that are bypassed when BCR signaling follows an alternate pathway produced by prior exposure of B cells to IL-4. The two pathways, classical and alternate, co-exist in IL-4-treated B cells. Here we report that operation of the IL-4-induced alternate ...

It has long been known that B cells produce autoantibodies and, thereby, contribute to the pathogenesis of many autoimmune diseases. Systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disorder, is characterized by high circulating autoantibody titers and immune-complex deposition that can trigger inflammatory damage in multiple ...

IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, and endothelial cells, promotes the growth of EBV-immortalized B cells in vitro and renders these cells tumorigenic in athymic mice. In the present study, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 ...

B cells are recognized as main actors in the autoimmune process. Autoreactive B cells can arise in the bone marrow or in the periphery and, if not properly inhibited or eliminated, can lead to autoimmune diseases through several mechanisms: autoantibody production and immune complex formation, ...

Autoreactive B cells are central in the pathogenesis of autoimmune diseases (AID) not only by producing autoantibodies but also by secreting cytokines and by presenting autoantigens. Changes in DNA methylation, histone modifications, and miRNA expression, the hallmarks of epigenetic failure, characterize B ...

Epstein-Barr virus (EBV) transformed human B cells proliferate indefinitely in vitro, and it has been proposed that cytokine-mediated autocrine loops contribute to the maintenance of the lymphoblastoid phenotype. We used a novel multiprobe RNase protection assay to quantify cytokine mRNA species expressed by ...

Genetically modified B cells are excellent tolerogenic antigen-presenting cells (APCs) in multiple models of autoimmunity. However, the mechanisms of action are still not completely understood. In our models, we generate antigen-specific tolerogenic B cells by transducing na�ve or primed B ...

OBJECTIVES: B cells have an impact on the perpetuation of chronic inflammatory or autoimmune diseases by multiple ways. A role for B cells as antigen presenting cells (APC) in the pathogenesis of chronic arthritis in humans has been suggested, however, the presence of such B ...

Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1(-/-) mice display ...

Kawasaki disease is an acute febrile illness of infancy and early childhood. Fifteen percent to 25% of children afflicted with Kawasaki disease develop coronary artery aneurysms. The acute phase of Kawasaki disease is characterized by a deficiency of suppressor T cells and the marked activation of T cells, B cells, and monocytes associated with increased ...

Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Several studies have shown decreased release in vitro of interleukin-2 (IL-2) following blood loss. To better define in vivo the interactions between T and B cells, as well as the effects of treatment with the T ...

Anaplastic Large Cell Lymphoma; Cutaneous B-Cell Non-Hodgkin Lymphoma; Mucosa-Associated Lymphoid Tissue Lymphoma; Intraocular Lymphoma; Monocytoid B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; ...

Nucleic acid sequences containing unmethylated CpG dinucleotides that modulate an immune response including stimulating a Th1 pattern of immune activation, cytokine production, NK lytic activity, and B cell proliferation are disclosed. The sequences are a...

A new mathematical model for IL-4 binding and internalization kinetics by high affinity receptors on the surface of T and B cells is described. This model is based on the hypothesis that two types of specific surface receptors to cytokines (or conformatio...

This book contains eight sections, each consisting of several papers. The section titles are: T-Cell Growth and Differentiation; B Cell Growth and Differentiation; Macrophage Regulation; Growth Factors; Lymphokines and Cytokines; Gene Cloning and Gene Regulations; Clinical Applications of Lymphokines; and Overview and Conclusions.

We studied the immune functions of two patients with angioimmunoblastic lymphadenopathy (AILD) in an attempt to determine whether the B cells were primarily hyperactive or, rather, if T cell abnormalities might underlie the B cell hyperactivity observed in these patients. We found that the ...

-infected cell (Janeway et al., 1999). Similarly, for B cells to be stim- ulated by helper T cells, interleukin-4 and segregation of cell surface molecules that form the immunological synapse and indicate a balance between sig that cytokines produced during helper T cell�B cell association ...

Elderly people show a reduced protection against new infections and a decreased response to vaccines as a consequence of impairment of both cellular and humoral immunity. In this paper we have studied memory/na�ve B cells in the elderly, evaluating surface immunoglobulin expression, production of the pro- and anti-inflammatory ...

B-cell-directed therapy-the use of agents that eliminate B cells or block cytokines important for B-cell function-is emerging as a promising approach to the treatment of rheumatic disease. Target diseases, including systemic lupus erythematosus (SLE), display diverse patterns of autoantibody production and aberrant ...

The presence of autoantibodies in New Zealand Black (NZB) mice suggests a B cell tolerance defect however the nature of this defect is unknown. To determine whether defects in B cell anergy contribute to the autoimmune phenotype in NZB mice, soluble hen egg lysozyme (sHEL) and anti-HEL Ig transgenes were bred onto ...

The peripheral B cell prosurvival cytokine BAFF/B lymphocyte stimulator (BLyS) has been proposed to participate in the regulation of immunological tolerance. Selective elimination or reconstitution of B cells expressing transgene-encoded, autoreactive BCRs upon systemic BLyS depletion or ...

Chronic immune activation in HIV-infected individuals leads to accumulation of exhausted tissue-like memory B cells. Exhausted lymphocytes display increased expression of multiple inhibitory receptors, which may contribute to the inefficiency of HIV-specific antibody responses. Here, we show that downregulation of B ...

Chronic immune activation in HIV-infected individuals leads to accumulation of exhausted tissue-like memory B cells. Exhausted lymphocytes display increased expression of multiple inhibitory receptors, which may contribute to the inefficiency of HIV-specific antibody responses. Here, we show that downregulation ...

IntroductionSystemic lupus erythematosus (SLE) is characterized by B cell hyper-activation and auto-reactivity resulting in pathogenic auto-antibody generation. The phenotypic analysis of blood B cell subsets can be used to understand these alterations.MethodsThe combined detection of CD19, CD27 and IgD (or IgM) by ...

S1P1 receptor expression is required for the egress of newly formed T cells from the thymus and exit of mature T and B cells from secondary lymphoid organs. In this study, we deleted the expression of the S1P1 receptor gene (S1pr1) in developing B cells in the bone marrow. Although B ...

S1P1 receptor expression is required for the egress of newly formed T cells from the thymus and exit of mature T and B cells from secondary lymphoid organs. In this study, we deleted the expression of the S1P1 receptor gene (S1pr1) in developing B cells in the bone marrow. Although B ...

Chronic inflammation characterized by T cell and macrophage infiltration of visceral adipose tissue (VAT) is a hallmark of obesity-associated insulin resistance and glucose intolerance. Here we show a fundamental pathogenic role for B cells in the development of these metabolic abnormalities. B ...

The pathogenesis of lupus nephritis is mainly attributable to a complex interaction between the innate and adaptive immune systems, including T and B cell function abnormalities. In addition to autoantibody production and immune complex deposition, Th1 and Th17 cytokines may play key roles in the development and ...

B lymphocytes are part of the inflammatory cells recruited to the human kidney in various disease settings. B cell infiltrates have been described in renal allografts, in acute and chronic interstitial nephritis, and the most common glomerular diseases like immunoglobulin A (IgA) and membranous nephropathy. These cells are almost exclusively recruited to ...

The relationship between class switch recombination (CSR) and somatic hypermutation has been unclear. By using human CD27(-) naive B cells, we investigated the somatic hypermutation and producibility of immunoglobulins (Igs) that occur after CSR. Although neither adult CD27(-) nor cord blood B cells, which showed ...

The chemokine CXCL12 induces prolonged focal adhesion kinase (FAK) phosphorylation and sustained proadhesive responses in progenitor bone-marrow (BM) B cells, but not in mature peripheral B cells. Here we demonstrate that suppressor of cytokine signaling 3 (SOCS3) regulated CXCL12-induced FAK ...

Intercellular communication is an essential process in stimulating lymphocyte development and in activating and shaping an immune response. B cell development requires cell-to-cell contact with and cytokine production by bone marrow stromal cells. However, this intimate relationship also may be responsible for the transfer of ...

During T cell�dependent responses, B cells can either differentiate extrafollicularly into short-lived plasma cells or enter follicles to form germinal centers (GCs). Interactions with T follicular helper (Tfh) cells are required for GC formation and for selection of somatically mutated GC B cells. Interleukin ...

CXCR4 expression is critical for localization of centroblasts in the dark zone of germinal centers (GCs), and centrocytes downregulate CXCR4 and thus leave the dark zone to reside in the light zone. However, mechanisms governing CXCR4 downregulation on centrocytes are not known. In this study, we show that the amount of intracellular CXCR4 in centroblasts was similar to that in centrocytes, ...

CD180 is homologous to TLR4 and regulates TLR4 signaling, yet its function is unclear. We report that injection of anti-CD180 mAb into mice induced rapid Ig production of all classes and subclasses, with the exception of IgA and IgG2b, with up to 50-fold increases in serum IgG1 and IgG3. IgG production after anti-CD180 injection was not due to reactivation of memory B ...

While B cells are generally considered to be positive regulators of humoral immune responses due to their ability to differentiate into plasmablasts/plasma cells and produce antibodies, B cells also modulate immune responses through antigen presentation and cytokine secretion. Moreover, ...

IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a ...

Within T cell�rich areas of secondary lymphoid organs, interdigitating dendritic cells recruit antigen-specific T cells that then induce B cells to secrete Igs. This study investigates the possible role(s) of dendritic cells in the regulation of human B cell responses. In the absence of exogenous ...

BackgroundThe incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 ...

Basic helix-loop-helix E proteins play critical roles in B cell development by stimulating B cell specific gene expression and immunoglobulin gene rearrangement. The function of E proteins can be effectively suppressed by their naturally occurring inhibitors, Id1 to 4. Ectopic expression of Id1 has been shown to ...

Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell�activating factor (BAFF) levels in patients with cGVHD suggest that B cells ...

Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects primarily the joints and without proper treatment results in their progressive destruction. In addition to T-cells, B-cells play a central role in the pathogenesis of this disease. The synovial tissue is an active site of B-cell accumulation, plasma cell differentiation and in situ antibody-production in ...

Autoantibody production is a hallmark of autoimmune diseases, such as lupus and rheumatoid arthritis. Accumulating evidence suggests a role of invariant NKT (iNKT) cells in their pathogenesis. Mechanisms underlying the role of iNKT cells in these diseases, however, remain unclear. In this study, we show that iNKT cells suppress IgG anti-DNA Ab and rheumatoid factor production and reduce ...

The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were ...

AML relapsing as ALL has rarely been reported. We describe the case of a 62-yr-old man who was diagnosed with erythroleukemia with a complex karyotype and achieved complete hematologic and cytogenetic remission after induction chemotherapy. However, 4 months after the initial diagnosis, he showed relapse with blasts showing a different morphology and immunophenotype and was diagnosed with ...

Signals delivered to B cells via CD40 can synergize with those provided by other B cell surface receptors to induce B cell proliferation and antibody class switching as well as modulate cytokine production and cell adhesion. Recently, it has been shown ...

STAT1 is a key effector of cytokines involved in the resistance to pathogens; its identified transcriptional targets mediate the innate immune response involved in the defense against viruses and bacteria. Little is known about the role of STAT1 in adaptive immunity, including its impact on BCR or surface Ig expression. Analysis of this point is difficult in humans, as STAT1 ...

Intercellular communication is an essential process in stimulating lymphocyte development and in activating and shaping an immune response. B celldevelopment requires cell-to-cell contact with and cytokine production by bone marrow stromal cells. However, this intimate relationship also may be responsible for the transfer of death-inducing molecules to the ...

B cells sense microenvironments through the B cell receptor (BCR) and Toll-like receptors (TLRs). While signals from BCR and TLRs synergize to distinguish self from nonself, inappropriate regulation can result in development of autoimmune disease. Here we show that CD22, an inhibitory co-receptor of BCR, also ...

Systemic administration of Salmonella to tumor-bearing mice leads to the preferential accumulation within tumor sites and retardation of the tumor growth. Host factors including innate and adaptive immune responses influence Salmonella-induced antitumor activity. Antitumor activities of Salmonella are not only determined by the tumor regression but also by the host immune response. Herein, we ...

The dynamics of cytokine content and the total protein and nonprotein forms of nitrogen in tissues of wintering organs of clary sage Salvia sclarea L. and cinquefoil Potentilla alba L. in abnormally cold (2005-2006 years) and abnormally warm (2006-2007 years) winters in Moscow have been studied. A direct correlation between the content ...

Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB (Fc?RIIB) are associated with the development of immunoglobulin (Ig) G serum autoantibodies and systemic autoimmunity in mice and humans. We used Ig gene cloning from single isolated B cells to examine the checkpoints that regulate development of ...

Impaired immune functions leading to primary immunodeficiencies often correlate with paradoxical autoimmune complications; patients with hyper-IgM syndromes who are deficient in activation-induced cytidine deaminase (AID), which is required for class-switch recombination and somatic hypermutation, are prone to develop autoimmune diseases. To investigate the impact of AID-deficiency on early ...

Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. ...

Myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG) are caused by autoantibodies against nicotinic acetylcholine receptor (AChR) in skeletal muscle. The production of anti-AChR antibodies is mediated by cytokines produced by CD4+ and CD8+ T helper (Th) cells. Emerging investigations of the roles of cytokines in MG ...

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy with a well recognized propensity for aggressive bone erosions. In some individuals, however, periarticular bone mineralization is maintained, and there is often associated new bone formation with periostitis and frank ankylosis; thus PsA manifests, in different individuals, reciprocal patterns of joint pathology suggesting a disorder ...

Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Steatosis, independently of its metabolic or viral origin, leads to liver injury and fibrosis. There are suggestions that hepatitis C virus may contribute to a wide spectrum of metabolic disturbances-namely, steatosis, insulin resistance, increased ...

The RecQ family helicase BLM is critically involved in the maintenance of genomic stability and BLM mutation causes the heritable disorder, Bloom�s syndrome. Affected individuals suffer from a predisposition to a multitude of cancer types and an ill-defined immunodeficiency involving low serum antibody titers. To investigate its role in B cell biology, ...

The RecQ family helicase BLM is critically involved in the maintenance of genomic stability, and BLM mutation causes the heritable disorder Bloom's syndrome. Affected individuals suffer from a predisposition to a multitude of cancer types and an ill-defined immunodeficiency involving low serum Ab titers. To investigate its role in B cell biology, we ...

The persistent environmental contaminant and immunotoxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), markedly suppresses humoral immune responses. We recently reported impaired down-regulation of paired box 5 (Pax5), a repressor of B cell differentiation and concomitant suppression of the immunoglobulin M (IgM) response by TCDD in the murine CH12.LX ...

BackgroundAllergic disease can be characterized as manifestations of an exaggerated inflammatory response to environmental allergens triggers. Mite allergen Der-p2 is one of the major allergens of the house dust mite, which contributes to TLR4 expression and function in B cells in allergic patients. However, the precise mechanisms of Der-p2 on ...

BackgroundThe etiologic agent of Chagas Disease is Trypanosoma cruzi. Acute infection results in patent parasitemia and polyclonal lymphocyte activation. Polyclonal B cell activation associated with hypergammaglobulinemia and delayed specific humoral immunity has been reported during T. cruzi infection in experimental mouse models. Based on preliminary ...

We previously demonstrated that the majority (? 90%) of porcine ileal Peyer's patch (IPP) follicular cells are immature B cells destined to die by apoptosis, when incubated at 37�. In this paper we approached the mechanisms responsible for positive selection of porcine IPP follicular immature B?cell selection, by screening for ...

Background. We have shown that approximately 30% of human peripheral blood B-cells express CD25. B cells expressing CD25 display a mature phenotype belonging to the memory B-cell population and have a better proliferative and antigen-presenting capacity. The aim of the present study was to characterize the ...

Rodent models have been extensively utilized to identify putative human immunotoxicants; however, even when immunotoxicity is established, uncertainty remains whether the effects are predictive of human risk. Therefore, the objective of this study was to establish a polyclonal immunoglobulin M (IgM) antibody-forming cell (AFC) response model to directly characterize immunotoxicity in primary mouse ...

Rodent models have been extensively utilized to identify putative human immunotoxicants; however, even when immunotoxicity is established, uncertainty remains whether the effects are predictive of human risk. Therefore, the objective of this study was to establish a polyclonal immunoglobulin M (IgM) antibody-forming cell (AFC) response model to directly characterize immunotoxicity in primary mouse ...

Lyn kinase deficient mice represent a well established genetic model of autoimmune/autoinflammatory disease that resembles systemic lupus erythematosus. We report that IL-10 plays a crucial immunosuppressive role in this model, modulating the inflammatory component of the disease caused by myeloid and T-cell activation. Double-mutant lyn(-/-)IL-10(-/-) mice manifested severe splenomegaly and ...

Systemic lupus erythematosus (SLE) persists as a chronic inflammatory autoimmune disease and is characterized by the production of autoantibodies and immune complexes that affect multiple organs. The underlying mechanism that triggers and sustains disease are complex and involve certain susceptibility genes and environmental factors. There have been several immune mediators linked to SLE including ...

Systemic lupus erythematosus (SLE) persists as a chronic inflammatory autoimmune disease and is characterized by the production of autoantibodies and immune complexes that affects multiple organs. The underlying mechanism that triggers and sustain disease are complex and involves certain susceptibility genes and environmental factors. There have been several immune mediators linked to SLE ...

Introgression of a New Zealand Black (NZB) chromosome 13 interval onto a C57BL/6 (B6) background (B6.NZBc13) is sufficient to produce many hallmarks of lupus, including high-titre anti-chromatin antibody production, abnormal B- and T-cell activation, and renal disease. In this study we sought to characterize the immune defects leading to these ...

Introgression of a New Zealand Black (NZB) chromosome 13 interval onto a C57BL/6 (B6) background (B6.NZBc13) is sufficient to produce many hallmarks of lupus, including high-titre anti-chromatin antibody production, abnormal B- and T-cell activation, and renal disease. In this study we sought to characterize the immune defects leading to these ...

Mice homozygous for the gene lpr develop marked lymphadenopathy and a spectrum of autoantibodies closely resembling that of human systemic lupus erythematosus. The unusual T cell phenotype of the expanded lymphocyte population and the T-dependence of several antibodies in this strain have suggested that primary T cell abnormalities underlie the autoimmune syndrome. Using ...

IntroductionDysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE), a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE.MethodsPhospho-specific ...

Cytokines are important in the regulation of the immune system and are secreted by a variety of cells in response to self and non-self stimuli. Communication within cells, in the same or distant anatomical sites, occurs via cytokines which determine the quality and intensity of inflammatory and adaptive immune responses. Infection by helminths is ...

IgE synthesis results from a complex interaction between T cells, B cells, and allergen presenting cells under the control of T cell and mast cell-/basophil-derived cytokines (IL-4, IL-5, and IL-6). IL-4 provides a first and crucial signal, which does not, however, suffice for the induction of IgE synthesis by human ...

In vitro and in vivo experimental data have pointed to new immunopathogenic mechanisms in primary Sj�gren's syndrome (pSS). The availability of targeted treatment modalities has opened new ways to selectively target these mechanistic pathways in vivo. This has taught us that the role of proinflammatory cytokines, in particular TNF?, is not crucial in the immunopathogenesis ...

Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Although mammary glands are the final target of infection, Peyer's patches (PP) are the entry site of the virus. Herein, we show that the infection induces increases in the number of PP IgA(+) B cells and higher ...

Porphyromonas gingivalis cysteine proteinases (gingipains) have been associated with virulence in destructive periodontitis, a disease process that has been linked with Th2 pathways. Critical in maintaining Th2 activity is the response of B lymphocytes to environmental interleukin (IL)-4, a cytokine that also counteracts Th1-cell differentiation. Here we demonstrate that while ...

Lymphatic filariasis is a disease characterized by immune dysregulation involving APC and T cell populations. To assess the contribution of TLR in mediating this dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B cells and monocytes of filaria-infected and uninfected individuals. Baseline expression of TLR was significantly lower ...

SUMMARY: Systemic lupus erythematosus (SLE) is a complex immune disorder in which loss of tolerance to nucleic acid antigens and other cross-reactive antigens is associated with the development of pathogenic autoantibodies that damage target organs including the skin, joints, brain, and kidney. B cells are essential to lupus pathogenesis, not only because ...

B-cells can contribute to the pathogenesis of autoimmune diseases not only through auto-antibody secretion but also via cytokine production. Therapeutic depletion of B-cells influences the functions and maintenance of various T-cell subsets. The mechanisms governing the functional heterogeneity of B-cell subsets as cytokine-producing ...

The CD1d-binding glycolipid ?-galactosylceramide exerts potent adjuvant effects on T-dependent humoral immunity. The mechanism is driven by cognate interaction between CD1d-expressing B cells and TCR-expressing type I CD1d-restricted NKT cells. Thus, far positive effects of alpha-galactosylceramide have been observed on initial and sustained antibody ...

Engagement of cytokine receptors by specific ligands activate Janus kinase�signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell ...

Previous studies using cell transfers and antibody receptor knockout mice have shown that B cells and antibodies are not essential components of the expulsion mechanism in Trichuris muris infections. Serum transfer experiments have given mixed results regarding the importance of antibodies in this infection model, and the role of B ...

A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var. coloratum agglutinin, VCA), which is known for its anti-cancer activity, was isolated from Korean mistletoe. In this study, IEC-6 rat intestinal epithelial cells and IM-9 human B-cells were cultured to determine the effect of VCA on cytokine and immunoglobulin (Ig) secretion. ...

Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of ...

Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of ...

Basic helix-loop-helix E proteins play critical roles in B-cell development by stimulating B cell-specific gene expression and immunoglobulin gene rearrangement. The function of E proteins can be effectively suppressed by their naturally occurring inhibitors, Id1 to 4. Ectopic expression of Id1 has been shown to block B-cell ...

Abnormalities in humoral immunity typically reflect a generalized or selective failure of effective B-cell development. The developmental processes can be followed through analysis of cell-surface markers, such as IgM, IgD, CD10, CD19, CD20, CD21, and CD38. Early phases of B-cell development are devoted to the creation of immunoglobulin and testing of ...

AimTo define prognostic significance of B-cell differentiation genes encoding proteins and BCL2 and BCL6 gene abnormalities in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern.MethodsIn 53 patients with diffuse large B-cell lymphoma and 20 patients with follicular lymphoma grade 3 ...

The chimeric anti-CD20 monoclonal antibody rituximab has become part of the standard therapy for patients with non-Hodgkin's lymphoma (NHL). To date, more than 300 000 patients have been treated with rituximab worldwide, including patients with indolent and aggressive NHL, Hodgkin's disease and other B-cell malignancies. Combination of rituximab with cytotoxic agents or ...

BackgroundUntreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced na�ve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African ...

The ligand for CD40 (CD40L) is a membrane glycoprotein on activated T cells that induces B cell proliferation and immunoglobulin secretion. Abnormalities in the CD40L gene were associated with an X-linked immunodeficiency in humans [hyper-IgM (immunoglobulin M) syndrome]. This disease is characterized by elevated concentrations of ...

The transcription factor Bright up-regulates immunoglobulin heavy chain production from select variable region promoters and requires Bright dimerization, Bruton�s tyrosine kinase (Btk) and the Btk substrate, TFII-I for this activity. Defects in Btk cause X-linked immunodeficiency disease in mice and man. Btk-deficient mice exhibit decreased serum IgM production, B ...

SummaryMutations in the btk gene encoding Bruton�s tyrosine kinase cause X-linked immune deficiency (XID), with impaired B-lymphocyte function as the major phenotype. Earlier we demonstrated that CBA/N-xid mice, unlike the wild type CBA mice, were not protected by BCG vaccination against tuberculosis (TB) infection. Since IFN-?-producing T-cells and activated macrophages are key elements of ...

In vitro experiments have documented the role of cytokines in the regulation of the human humoral immune response. Which cytokines are operative in vivo and in which lymphoid compartment interactions between cytokine-producing T cells and antibody-forming B cells occur is still unclear. For ...

In vitro experiments have documented the role of cytokines in the regulation of the human humoral immune response. Which cytokines are operative in vivo and in which lymphoid compartment interactions between cytokine-producing T cells and antibody-forming B cells occur is still unclear. For ...

In the present report, we revisited the B cell responsiveness of 7 wild-derived mouse strains to various toll-like receptor ligands (TLR-L). We found that 2 of them, namely PWK and STF presented profound defects in B cell proliferative responses to most of the TLR-L. Yet, their macrophage responses were largely ...

T cell Ig domain and mucin domain protein 1 (TIM-1) is a costimulatory molecule that regulates immune responses by modulating CD4+ T cell effector differentiation. However, the function of TIM-1 on other immune cell populations is unknown. Here, we show that in vivo in mice, TIM-1 is predominantly expressed on B rather than T cells. Importantly, TIM-1 was expressed by a large majority of ...

T cell Ig domain and mucin domain protein 1 (TIM-1) is a costimulatory molecule that regulates immune responses by modulating CD4⁺ T cell effector differentiation. However, the function of TIM-1 on other immune cell populations is unknown. Here, we show that in vivo in mice, TIM-1 is predominantly expressed on B rather than T cells. Importantly, TIM-1 was expressed by a ...

FoxP3(+) T cells play critical roles in the regulation of B-cell function and humoral immune response. FoxP3(+) T cells migrate to the T and B zones of lymphoid organs and the border area between the two areas. Not only can FoxP3(+) T cells suppress B cells directly, but they also suppress B-cell response indirectly through suppressing ...

Pasteurella multocida is a Gram-negative bacillus that infects a number of wild and domestic animals, causing respiratory diseases. Toxigenic Pasteurella multocida strains produce a protein toxin (PMT) that leads to atrophic rhinitis in swine due to enhanced osteoclastogenesis and the inhibition of osteoblast function. We show that PMT-induced osteoclastogenesis is promoted by an ...

Pasteurella multocida is a Gram-negative bacillus that infects a number of wild and domestic animals, causing respiratory diseases. Toxigenic Pasteurella multocida strains produce a protein toxin (PMT) that leads to atrophic rhinitis in swine due to enhanced osteoclastogenesis and the inhibition of osteoblast function. We show that PMT-induced osteoclastogenesis is promoted by an ...

IL-10 plays a central role in restraining the vigor of inflammatory responses, but the critical cellular sources of this counter-regulatory cytokine remain speculative in many disease models. Using a novel IL-10 transcriptional reporter mouse, we found an unexpected predominance of B cells (including plasma cells) among ...

IL-10 plays a central role in restraining the vigor of inflammatory responses, but the critical cellular sources of this counter-regulatory cytokine remain speculative in many disease models. Using a novel IL-10 transcriptional reporter mouse, we found an unexpected predominance of B cells (including plasma cells) among IL-10 ...

The evidence of a tight spatial interaction between mast cells (MCs) and B lymphocytes in secondary lymphoid organs, along with the data regarding the abundance of MCs in several B-cell lymphoproliferative disorders prompted us to investigate whether MCs could affect the proliferation and differentiation of B cells. To this aim, we ...

Early B cell factor (EBF) is a transcription factor essential for specification and commitment to the B cell fate. In this study, we show downregulation of a developmentally regulated cluster of hoxa genes, notably hoxa9, coincides with induction of EBF at the Pro-B cell ...

Hypomorphic RAG mutations, leading to limited V(D)J rearrangements, cause Omenn syndrome (OS), a peculiar severe combined immunodeficiency associated with autoimmune-like manifestations. Whether B cells play a role in OS pathogenesis is so far unexplored. Here we report the detection of plasma cells in lymphoid organs of OS patients, in which circulating ...

The inflammatory cytokine TNF-? has been recognized as a critical tumor promoter, but the effector cells that mediate its action have not been fully characterized. Because B cells regulate squamous and prostate carcinogenesis, and Tnf(-/-) mice harbor B-cell defects, we investigated the hypothesis that ...

After many years of debate, there is now general agreement that B cells can participate in the immune response to cardiac transplants. Acute antibody-mediated rejection (AMR) is the best defined manifestation of B cell responses, but diagnostic and mechanistic questions still surround AMR. Many complement dependent ...

Stimulation of human B cells with anti-CD40 + interleukin-4 (IL-4) results not only in proliferation and immunoglobulin E (IgE)-production, but also increased production of the cytokine lymphotoxin-alpha (LT-alpha) (formerly also known as tumour necrosis factor-beta (TNF-beta)). Here, we studied the role of LT-alpha (TNF-beta) in ...

B cells play an important role in the pathogenesis of both systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce autoantibodies, but also are capable to efficiently present specific autoantigens to T cells. Furthermore, B cells can secrete ...

The aim of the present study was to determine whether different subsets of B cells characterize synovial fluid (SF) or tissue (ST) of seropositive or seronegative rheumatoid arthritis (RA) with respect to the peripheral blood (PB). PB, SF and ST of 14 autoantibody (AB) positive (RF-IgM, RF-IgA, anti-CCP), 13 negative RA and 13 non-RA chronic arthritides ...

Natural antibodies are autoreactive/polyreactive antibodies believed to be secreted in the absence of xenoantigens. The origin and functional role of this limited and selective autoimmunity are not clear, nor is the specificity and range of autoantigens that drive the development of B cells producing natural antibodies. In this issue of the JCI, Merbl et ...

Our earlier results indicate that peritoneal B cells (PEB cells) were not hyporesponsive to in vitro crosslinking of the immunoglobulin (Ig) with a secondary anti-IgG reagent. In this study, the response of PEB cells was reduced by the same treatment given i.p. PEB cells were only sensitive to anti-IgM hyper-crosslinking in the presence of peritoneal ...

Various therapeutic options using cytokines have been described in the treatment of melanoma, T cell lymphoma, B cell lymphoma, squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma. The treatment regimens include cytokine substitution, cytokine induction, ...

Human and canine lymphoid neoplasms are characterized by non-random cytogenetic abnormalities. However, due to the low mitotic activity of the B cells, cytogenetic analyses of B-cell lymphoid proliferations are difficult to perform. In the present study we stimulated canine B-cell lymphoma cells with the ...

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with involvement of both B cells and cytotoxic T lymphocytes and several cytokines aberrations. Standard therapy for SLE has its limitations. Tacrolimus, a novel calcineurin inhibitor with potent immunosuppressive effects, has been shown in the recent years to ...

Cytokines play an important role in the immune system, and abnormalities in their production have been found in many human diseases. Interleukin-21 (IL-21), a type I cytokine produced by activated T cells, has diverse effects on the immune system, but its ability to induce production of other cytokines is not well ...

In this study, we have evaluated the production of pro- and anti-inflammatory cytokines and the formation of central and effector memory T cells in mice lacking mature B cells (muMT KO). The results show that Trypanosoma cruzi infection in C57Bl/6m? MT KO mice is intensified in relation to control mice and this exacerbation is related ...

Aims In recent years the genetic aberrations associated with diffuse large B-cell lymphoma and the new subtype described in the 2008 revision of the WHO classification, 'B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma' have been increasingly well defined. Recurrent ...

BAFF (B lymphocyte activating factor of the tumour necrosis factor family) is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. Increased serum levels of BAFF are found in a number of different autoimmune diseases, and BAFF is found in inflammatory sites in which there is lymphoid ...

Cytokines have a major role in promoting the growth and spread of cancers. Elevated levels of several cytokines have been described in cancer patients. Evidence from animal and human studies suggests that cytokines may contribute to a wide range of symptoms in advanced cancer, including: asthenia, pain, drowsiness, cognitive failure, ...

BACKGROUND:Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co?infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment.OBJECTIVE:To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1.METHODS:Lung specimens underwent ...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease leading to inflammatory tissue damage in multiple organs (e.g., lupus nephritis). Current treatments including steroids, antimalarials, and immunosuppressive drugs have significant side effects. Activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version has been approved by ...

BackgroundDysfunction of the immune system has been documented in many types of cancers. The precise nature and molecular basis of immune dysfunction in the cancer state are not well defined.Methods and FindingsTo gain insights into the molecular mechanisms of immune dysfunction in cancer, gene expression profiles of pure sorted peripheral blood lymphocytes from 12 patients with melanoma were ...