title: The imperfect control of self-reactive germinal center B cells.
abstract: Unlike T cells, B cells diversify their antigen receptor (BCR) binding specificities at two distinct stages of differentiation. Thus, in addition to initial variable region gene rearrangements, B cells recruited into T-dependent immune responses further modify their BCR specificity via iterative rounds of somatic hypermutation (SHM) within germinal centers (GCs). Although critical for providing the high-affinity antibody specificities required for long-term immune protection, SHM can also generate self-reactive B cells capable of differentiating into autoantibody-producing plasma cells. Recent data confirm that self-reactive GC B cells can be effectively removed from the secondary repertoire so as to maintain self-tolerance. However, they can also escape deletion under certain circumstances and so contribute to autoimmune disease via production of somatically mutated, pathogenic autoantibodies.
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Australia, Darlinghurst, NSW 2010, Australia. Electronic address: r.brink@garvan.org.au.
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D001323:Autoantibodies; D001324:Autoantigens