B cell tolerance--how to make it and how to break it.
A series of checkpoints for antigen receptor fitness and specificity during B cell development ensures the elimination or anergy of primary, high-avidity-autoantigen-reactive B cells. Defects in genes encoding molecules with which this purging of the original B cell repertoires is achieved may break this B cell tolerance, allowing the development of B cell- and autoantibody-mediated immune diseases. Furthermore, whenever tolerance of helper T cells to a part of an autoantigen is broken, a T cell-dependent germinal center-type response of the remaining low--or no--autoreactive B cells is activated. It induces longevity of these B cells, and expression of AiD, which effects Ig class switching and IgV-region hypermutation. The development of V-region-mutant B cells and the selections of high-avidity-autoantigen-reactive antibodies producing B cells by autoantigens from them, again, can lead to the development and propagation of autoimmune diseases such as lupus erythematosus or chronic inflammatory rheumatoid arthritis by the autoantibody BcR-expressing B cells and their secreted autoantibodies.
Melchers
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Department of Cell Biology, Biozentrum, University of Basel, Switzerland. fritz.melchers@unibas.ch
Rolink
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D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology
D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D051193:Toll-Like Receptors