Effector B cells in autoimmune diseases

The advent of B-cell targeted agents has prompted reappraisal of the role of B cells in the pathogenesis of autoimmune diseases (AID). Most notably, pathogenic B cells not only are the source of antibodies but also function as potent effectors mainly via antigen presentation and costimulation, and release of pro-inflammatory cytokines. Along with recent findings showing the existence of regulatory B cells, the role of B cells in AID seems more complicated than previously thought. Autoreactive B cells normally remain innocuous by the multi-layered mechanisms of self-tolerance during ontogeny. Disruption of these mechanisms, however, leads to the development of AID, where pathogenic effector B cells are enriched in particular B cell subsets. Given risk/benefit considerations, a novel strategy to selectively target the function of effector B cells would be more preferable than the nonselective B-cell depletion achieved by anti-CD20 therapy in AID.