B Cell Receptor Rehabilitation--Pausing to Reflect

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Science  23 Feb 2001:
Vol. 291, Issue 5508, pp. 1503-1505
DOI: 10.1126/science.291.5508.1503

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Immunologists have long been fascinated by how the immune system gets rid of immature B cells carrying antibody against self antigens before they can do any real damage. Clonal deletion (death) and clonal anergy (disability) are two mechanisms for inducing tolerance to self antigens in order to avoid autoimmunity. Recently, a third more parsimonious mechanism, receptor editing, has been described. However, it has been difficult to reconcile how cell death and receptor editing can coexist as distinct tolerance mechanisms. Even more contentious has been defining the stage in B cell development where these processes take place. Now, according to King and Monroe in their Perspective, recent work by Casellas et al. may have shed some light on these issues. Self-reactive B cells pause during their development in the bone marrow and attempt to remove the offending antibodies without destroying or inactivating the developing B cells that bear them. Those that fail to accomplish this are likely doomed to die.