The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1999/5/1639/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 10, May 17, 1999 1639-1648


Articles

A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus

Owen T.M. Chan*, Lynn G. Hannum*, Ann M. Haberman{ddagger}, Michael P. Madaio§, and Mark J. Shlomchik*,{ddagger}

From the * Section of Immunobiology and the {ddagger} Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510; and the § Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

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.

Key Words: nephritis • transgenic • T cell • vasculitis • antigen presentation


Address correspondence to Mark J. Shlomchik, CB462, Department of Laboratory Medicine, 333 Cedar St., Box 208035, Yale University School of Medicine, New Haven, CT 06510-8035. Phone: 203-688-2089; Fax: 203-688-2748; E-mail: mark.shlomchik{at}yale.edu

Abbreviations used: dsDNA, double stranded DNA; GN, glomerulonephritis; IN, interstitial nephritis; mIgM, membrane IgM; NOD, nonobese diabetic; NP, (4-hydroxy-3-nitro-phenyl) acetyl; Tg, transgene; Tgic, transgenic.


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