title: B cell-independent contribution of BAFF to murine autoimmune disease.
abstract: BAFF blockade is efficacious in murine and human SLE. Whereas the attendant reduction in B cells contributes to the efficacy, it remains unresolved whether a B cell-independent component also contributes. Since accurate assessment of a B cell-independent component can only be made in a B cell-independent autoimmune disease, we investigated MOG35-55-induced EAE in C57BL/6 mice. Neither pharmacologic neutralization nor genetic elimination of BAFF affected disease, nor did elimination of APRIL (with or without elimination of BAFF) or constitutive over-expression of BAFF. Eliminating BAFF had no effect on disease even in mice that were genetically manipulated to maintain greater-than-normal numbers of B cells. However, elimination of BAFF in B cell-deficient mice dramatically reduced disease, thereby unmasking a B cell-independent contribution of BAFF to an autoimmune disease. Our findings raise the plausibility that BAFF contributes to SLE not only through effects on B cells but through B cell-independent pathways as well.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, United States. Electronic address: stohl@usc.edu.
authors.forename: William
authors.initials: W
authors.lastname: Stohl
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, United States.
authors.forename: Agnes
authors.initials: A
authors.lastname: Banfalvi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D053264:B-Cell Activating Factor; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: APRIL; B cells; BAFF; EAE; SLE; Transgenic mice