Abstract
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. Autoreactive B cells undergo stringent selection either in the bone marrow or peripheral circulation by deletion, 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. Discovering the precise nature of B-cell tolerance alterations in patients with autoimmune diseases will lead to the identification of new targets for therapeutic interventions in patients with these disorders.
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