Abstract
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.
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Melchers, F., Rolink, A.R. (2006). B Cell Tolerance—How to Make It and How to Break It. In: Radbruch, A., Lipsky, P.E. (eds) Current Concepts in Autoimmunity and Chronic Inflammation. Current Topics in Microbiology and Immunology, vol 305. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-29714-6_1
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DOI: https://doi.org/10.1007/3-540-29714-6_1
Publisher Name: Springer, Berlin, Heidelberg
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