Receptor Revision and Systemic Lupus

Studies over the past 10 years have shown that B cells can undergo secondary heavy‐ or light‐chain immunoglobulin (Ig) rearrangements at various stages of their normal development, a process termed receptor editing. In the bone marrow, this mechanism is important to maintain tolerance because it can extinguish a self‐reactive specificity without having to physically eliminate a potentially autoreactive B cell. In the periphery, secondary rearrangements may also play a role in the diversification and maturation of an immune response, although conclusive evidence for this process is still required. Individuals with systemic autoimmune diseases, such as lupus, show evidence of intricate abnormalities in receptor editing. On the one hand, decreased editing may not eliminate the self‐reactive specificities that emerge during B‐cell development in the bone marrow. Conversely, excessive secondary rearrangements, especially in the periphery where tolerance mechanisms are less effective, can result in the production of autoantibodies by edited B cells. It will be important to assess whether the complex editing defects observed during lupus are a primary susceptibility factor to this disease or if they are secondary to other abnormalities of lymphocyte development in these autoimmune patients.