title: Class switch recombination in B lymphopoiesis: a potential pathway for B cell autoimmunity.
abstract: 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.
authors.affiliation: Department of Immunology, Technion Faculty of Medicine, Haifa 31096, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Diamant
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
mesh_terms: 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
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019014:fas Receptor