The central and multiple roles of B cells in lupus pathogenesis

A standard view of B cells in systemic autoimmunity is that they promote lupus by producing autoantibodies (autoAb). Hoc-ever, this view is incomplete because recent studies have revealed that autoimmune disease can be dissociated from autoAb deposition. Furthermore, the spontaneous T-cell activation and organ infiltration in systemic lupus erythematosus patients and animal models are difficult to explain entirely via a direct autoAb-mediated mechanism. In this review we describe work addressing the B-cell functions of autoantigen presentation and autoAb production in lupus pathogenesis. In the J(H)D-MRL-Fas(lpr) strain (J(H)D/lpr), a B-cell-deficient version of the lupus-prone MRL-Fas(lpr) (MRL/lpr) mouse, spontaneous nephritis and dermatitis is abrogated, demonstrating that B cells have a primary role in disease. B cells play a similar role in Fas-intact, lupus-prone MRL mice. To address the role of autoantigen presentation, we analyzed transgenic mice which have B cells that cannot secrete immunoglobulin (mIgM transgenic mice). The restoration of B cells without antibody caused substantial interstitial nephritis and vasculitis although less marked than the intact MRL/lpr controls. To address the role of autoAb, we infused serum from aged MRL/lpr mice into J(H)D/lpr mice. At most, mild to no nephritis was observed in the infused mice. These results indicate that B cells are promoting autoimmunity in mechanisms other than autoAb secretion, and we describe a model depicting these B-fell roles in the context of other inflammatory events in lupus.