Class switch recombination in B lymphopoiesis: a potential pathway for B cell autoimmunity.
Pathogenic autoantibodies detected in autoimmune diseases are predominantly IgG isotypes, reflecting the generation and activation of an autoimmune memory B cell repertoire. It is not completely understood how such autoreactive cells are generated and escape central and/or peripheral tolerance mechanisms, and several models to explain this have been proposed. It is generally thought that B lymphocytes utilize IgM receptors for development and tolerance establishment, whereas IgG receptors are primarily used to promote memory formation and signal for memory-type responses. In here we review recent findings suggesting that spontaneously occurring class switch recombination in B lymphopoiesis confer B lymphocytes with a novel developmental pathway that is driven by non-IgM receptors. The physiological relevance of this developmental pathway in generating an autoimmune memory repertoire, as well as a Fas-dependent mechanism regulating it, is discussed.
Diamant
Eran
E
Department of Immunology, Technion Faculty of Medicine, Haifa 31096, Israel.
Melamed
Doron
D
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D038041:Lymphopoiesis / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019014:fas Receptor