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). However, 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 JHD-MRL-Faslpr strain (JHD/lpr), a B-cell-deficient version of the lupus-prone MRL-Faslpr (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 JHD/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-cell roles in the context of other inflammatory events in lupus.
Chan
O T
OT
Section of Immunobiology, Yale University School of Medicine, New Haven 06510, USA.
Madaio
M P
MP
Shlomchik
M J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology