B lymphocytes as therapeutic targets in systemic lupus erythematosus

In recent years, experimental evidence supporting a major role of B cells in the pathogenesis of autoimmune diseases has grown. This includes the discovery of novel mechanisms of autoantibody pathogenicity and the potential of B cells to mediate inflammation and tissue injury. In some instances, engagement of the B cell receptor and other surface receptors is sufficient to stimulate B cells to produce antibody. As a result, B cells have become targets for immunointervention. In lupus, targeting B cell activation factor (BAFF, BLys) indicates that specific blockade of this longevity factor might be sufficient to suppress systemic autoimmunity. Targeting CD20 represents another promising avenue for the treatment of refractory lupus in both adults and children. Although the clinical data add weight to the importance of B cells in the pathogenesis of lupus, new targets for B cell depletion therapy are being investigated. In experimental models, combining CD19 and CD20 antibodies was more effective than either treatment alone.