Mechanisms of Peripheral B Cell Tolerance

Abstract

Autoreactive B cells, which recognize antigens derived from the body's own tissues, make up roughly 20% of the B cells that reside in peripheral lymphoid organs. These include all tissues outside sites of B cell development. B cells develop primarily in the bone marrow, and when they first express antigen receptors, most (>70%) are autoreactive. Many of these immature autoreactive cells are purged by ‘central’ tolerance mechanisms known as receptor editing or clonal deletion. However, some escape and populate the periphery. These cells are silenced by several mechanisms, the major one being B cell anergy, in which the autoreactive cells are maintained in an antigen unresponsive state. Autoreactive B cells are also generated during active immune responses, during which they acquire immunoglobulin gene mutations that result in autoreactivity. This is thought to occur in germinal center reactions as a by-product of the somatic mutation process that serves to increase antibody affinity. Failure of central or peripheral tolerance mechanisms can result in autoimmunity. Here we review the mechanisms operative in maintaining tolerance of peripheral B cells.