B Cells in Systemic Lupus Erythematosus: From Disease Mechanisms to Targeted Therapies

B cells exert a prominent contribution to the pathogenesis of systemic lupus erythematosus (SLE). Here, we review the immune mechanisms underlying autoreactive B cell activation in SLE, focusing on how B cell receptor and Toll-like receptor signals integrate to drive breaks in tolerance to nuclear antigens. In addition, we discuss autoantibody-dependent and autoantibody-independent B cell effector functions during lupus pathogenesis. Finally, we address efforts to target B cells therapeutically in human SLE. Despite initial disappointing clinical trials testing B cell depletion in lupus, more recent studies show promise, emphasizing how greater understanding of underlying immune mechanisms can yield clinical benefits.