Distinct Role of Surface Lymphotoxin Expressed by B Cells in the Organization of Secondary Lymphoid Tissues

Tumanov, Alexei V.; Kuprash, Dmitry V.; Lagarkova, Maria A.; Grivennikov, Sergei I.; Abe, Koichiro; Shakhov, Alexander N.; Drutskaya, Ludmila N.; Stewart, Colin L.; Chervonsky, Alexander V.; Nedospasov, Sergei A.

doi:10.1016/s1074-7613(02)00397-7

Cited by 180 publications

(227 citation statements)

References 64 publications

Supporting

Mentioning

219

Contrasting

Order By: Relevance

“…Furthermore, the representations of B-cell subsets and the serum concentrations of Ig classes were unchanged at disease onset and during most of the disease course in AireϪ/Ϫ adults compared with wild-type littermates [(3, 24) and our unpublished data]. B cells can have a variety of functions: They produce Igs, release immunomodulatory cytokines, regulate lymphoid tissue neogenesis and lymphangiogenesis, present antigen, and influence the activities of dendritic cells and T cells (25)(26)(27)(28)(29). Of these functions, the production of Igs is central to certain other autoimmune disease models, for example, transfer of self-reactive Igs triggers the immediate onset of inflammatory immunopathology in arthritis, lupus nephritis, oophoritis, pemphigus, etc.…”

Section: Discussionmentioning

confidence: 99%

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

Gavanescu

Benoist

Mathis

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).autoimmunity ͉ B lymphocytes ͉ tolerance ͉ autoantibody

show abstract

Section: Discussionmentioning

confidence: 99%

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

Gavanescu

Benoist

Mathis

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Lymphotoxin ␤ (Ltb) was strongly down-regulated by anti-Ig (Fig. 6), an unexpected result given that Ltb produced by B cells is required for normal T-dependent humoral responses (60). A smaller magnitude of down-regulation was induced by IL-4.…”

Section: Gene Expression Change Patterns Distinguishing Anti-igmentioning

confidence: 91%

Analysis of the Major Patterns of B Cell Gene Expression Changes in Response to Short-Term Stimulation with 33 Single Ligands

Zhu

Hart

Chang

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

We examined the major patterns of changes in gene expression in mouse splenic B cells in response to stimulation with 33 single ligands for 0.5, 1, 2, and 4 h. We found that ligands known to directly induce or costimulate proliferation, namely, anti-IgM (anti-Ig), anti-CD40 (CD40L), LPS, and, to a lesser extent, IL-4 and CpG-oligodeoxynucleotide (CpG), induced significant expression changes in a large number of genes. The remaining 28 single ligands produced changes in relatively few genes, even though they elicited measurable elevations in intracellular Ca2+ and cAMP concentration and/or protein phosphorylation, including cytokines, chemokines, and other ligands that interact with G protein-coupled receptors. A detailed comparison of gene expression responses to anti-Ig, CD40L, LPS, IL-4, and CpG indicates that while many genes had similar temporal patterns of change in expression in response to these ligands, subsets of genes showed unique expression patterns in response to IL-4, anti-Ig, and CD40L.

show abstract

“…The positive regulatory roles of B cells extend to multiple immune system components; the absence of B cells during mouse development results in significant quantitative and qualitative abnormalities within the immune system, including a remarkable decrease in thymocyte numbers and diversity [12], significant defects within spleen dendritic cell and T cell compartments [13-15], absence of Peyer's patch organogenesis and follicular dendritic cell networks [16,17], and absence of marginal zone and metallophilic macrophages with decreased chemokine expression [15,17]. B cells also positively regulate lymphoid tissue organization [18,19]. Finally, dendritic cell, macrophage, and T H cell development may all be influenced by B cells during the formation of immune responses [20].…”

Section: Introductionmentioning

confidence: 99%

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

2013

View full text Add to dashboard Cite

B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of co-stimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and inflammation has been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specific IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through different mechanisms. B10 cells are a functionally defined subset currently identified only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defined B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an effective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity.

show abstract

Distinct Role of Surface Lymphotoxin Expressed by B Cells in the Organization of Secondary Lymphoid Tissues

Cited by 180 publications

References 64 publications

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

Analysis of the Major Patterns of B Cell Gene Expression Changes in Response to Short-Term Stimulation with 33 Single Ligands

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

Contact Info

Product

Resources

About