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J. Exp. Med.,
Volume 189, Number 10, May 17, 1999 1639-1648
By


From the * Section of Immunobiology and the 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.
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
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