Secondary receptor editing in the generation of autoimmunity

Abstract

Receptor editing is the process that replaces the heavy chain or light chain variable region genes in a B cell immunoglobulin receptor that is already productively rearranged. It is a major mechanism in the bone marrow for maintaining B cell tolerance to autoantigens. We propose that a pathological autoimmune process can use receptor editing to induce the de novo creation and activation of B cells with autoreactive receptors in the peripheral immune system.

Figure 1. BCR specificity dictates selective outcome at multiple checkpoints

B cells that interact avidly with soluble autoantigens are purged from the active repertoire at several stages of ontogeny by negative selection. We propose an additional process whereby mature B cells can acquire a new autoreactivity by receptor revision or somatic mutation [28]. The creation and survival of such autoreactive cells would depend on abnormal immunoregulation, such as ongoing T-cell help. (Figure modified from M.P. Cancro [29]).