B-cell tolerance checkpoint violations in systemic lupus erythematosus

Abstract

B cells play a crucial role in the pathogenesis of the prototypic autoimmune disease systemic lupus erythematosus. The presence of autoantibodies in lupus is indicative of a breach in B-cell tolerance to self. Studies conducted over the past 15 years indicate that tolerance checkpoints exist at various stages of B-cell development to ensure that self-reactive B cells are censored and do not produce autoantibodies. These include an early checkpoint operative at the immature B-cell stage in the bone marrow, with receptor editing and deletion as the two main mechanisms. Additional checkpoints exist in the periphery and include receptor revision and anergy at the mature naive stage, with further checkpoints being operative at the germinal center and memory B-cell stages. In a recent study, it has been shown that mice harboring the lupus susceptibility gene Sle1bz/Ly108z display defective tolerance both at the immature as well as the mature B-cell stage in the periphery. This, along with other studies conducte...