A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus.
The precise role of B cells in systemic autoimmunity is incompletely understood. Although B cells are necessary for expression of disease (Chan, O., and M.J. Shlomchik. 1998. J. Immunol. 160:51-59, and Shlomchik, M.J., M.P. Madaio, D. Ni, M. Trounstine, and D. Huszar. 1994. J. Exp. Med. 180:1295-1306), it is unclear whether autoantibody production, antigen presentation, and/or other B cell functions are required for the complete pathologic phenotype. To address this issue, two experimental approaches were used. In the first, the individual contributions of circulating antibodies and B cells were analyzed using MRL/MpJ-Faslpr (MRL/lpr) mice that expressed a mutant transgene encoding surface immunoglobulin (Ig), but which did not permit the secretion of circulating Ig. These mice developed nephritis, characterized by cellular infiltration within the kidney, indicating that B cells themselves, without soluble autoantibody production, exert a pathogenic role. The results indicate that, independent of serum autoantibody, functional B cells expressing surface Ig are essential for disease expression, either by serving as antigen-presenting cells for antigen-specific, autoreactive T cells, or by contributing directly to local inflammation.
D000818:Animals; D000906:Antibodies / Q000097:blood*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D008177:Lupus Vulgaris / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009393:Nephritis / Q000276:immunology; D009929:Organ Size; D010641:Phenotype; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology