Fate determination of mature autoreactive B cells.

A large antibody repertoire is generated in developing B cells in the bone marrow. Before these B cells achieve immunocompetence, those expressing autospecificities must be purged. To that end, B cells within the bone marrow and just following egress from the bone marrow are subject to tolerance induction. Once B cells achieve immunocompetence, the antibody repertoire can be further diversified by somatic hypermutation of immunoglobulin genes in B cells that have been activated by antigen and cognate T cell help and have undergone a germinal center (GC) response. This process also leads to the generation of autoreactive B cells which must be again purged to protect the host. Thus, B cells within the GC and just following egress from the GC are also subject to tolerance induction. Available data suggest that B cell intrinsic processes triggered by signaling through the B cell receptor activate tolerance mechanisms at both time points. Recent data suggest that GC and post-GC B cells are also subject to B cell extrinsic tolerance mechanisms mediated through soluble and membrane-bound factors derived from various T cell subsets.