Publications

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.