Are autoantibodies the targets of B-cell-directed therapy?

Autoantibodies, produced by autoreactive B cells, are involved in the pathology of rheumatic diseases including systemic lupus erythematosus (SLE). Modulation of B-cell function by inhibiting cytokines active on B cells or even eliminating B-cell populations can effectively treat SLE and other diseases. So far so simple, yet—as explored in this Perspective—the relationships between the effects of such therapies on B cells, the levels of individual autoantibodies, and clinical outcomes are fiendishly complex. Better knowledge of B-cell biology is needed to understand the effects of agents that target B cells, and to increase their efficacy.