A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus

OTM Chan, LG Hannum, AM Haberman… - The Journal of …, 1999 - rupress.org
OTM Chan, LG Hannum, AM Haberman, MP Madaio, MJ Shlomchik
The Journal of experimental medicine, 1999rupress.org
The precise role of B cells in systemic autoimmunity is incompletely understood. Although B
cells are necessary for expression of disease (Chan, O., and MJ Shlomchik. 1998. J.
Immunol. 160: 51–59, and Shlomchik, MJ, MP 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 …
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.
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