Regulation of autoreactive antibodies

Purpose of review Significant progress has been made over recent years in uncovering the B-cell tolerance mechanisms that control development of autoreactive antibodies. This review examines current knowledge on the regulation and selection of autoreactive B cells in mouse models, and in healthy humans and patients with autoimmune disorders. Recent findings Autoreactive B cells undergo stringent selection, the bone marrow or peripheral circulation by induction of anergy, or receptor editing. There is growing evidence that receptor editing represents the primary physiologic B-cell tolerance mechanism. Several checkpoints against autoreactive B cells have been established in bone marrow and peripheral blood of healthy humans. Recent studies demonstrate that some autoimmune disorders are associated with several alterations in B-cell tolerance checkpoints and often lead to a greater number of autoreactive B cells in the, circulation. Summary Discovering the precise nature of B-cell tolerance alterations in patients with autoimmune disease will lead to the identification of new targets for therapeutic interventions in patients with these disorders.