TY - JOUR
T1 - A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus
AU - Chan, Owen T.M.
AU - Hannum, Lynn G.
AU - Haberman, Ann M.
AU - Madaio, Michael P.
AU - Shlomchik, Mark J.
PY - 1999/5/17
Y1 - 1999/5/17
N2 - 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-Fas(lpr) (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.
AB - 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-Fas(lpr) (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.
KW - Antigen presentation
KW - Nephritis
KW - T cell
KW - Transgenic
KW - Vasculitis
UR - http://www.scopus.com/inward/record.url?scp=0033577903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033577903&partnerID=8YFLogxK
U2 - 10.1084/jem.189.10.1639
DO - 10.1084/jem.189.10.1639
M3 - Article
C2 - 10330443
AN - SCOPUS:0033577903
SN - 0022-1007
VL - 189
SP - 1639
EP - 1647
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -