Cutting edge: a role for CD1 in the pathogenesis of lupus in NZB/NZW mice.
Since anti-CD1 TCR transgenic T cells can activate syngeneic B cells via CD1 to secrete IgM and IgG and induce lupus in BALB/c mice, we studied the role of CD1 in the pathogenesis of lupus in NZB/NZW mice. Approximately 20% of B cells from the spleens of NZB/NZW mice expressed high levels of CD1 (CD1high B cells). The latter subset spontaneously produced large amounts of IgM anti-dsDNA Abs in vitro that was up to 25-fold higher than that of residual CD1int/low B cells. T cells in the NZB/NZW spleen proliferated vigorously to the CD1-transfected A20 B cell line, but not to the parent line. Treatment of NZB/NZW mice with anti-CD1 mAbs ameliorated the development of lupus. These results suggest that the CD1high B cells and their progeny are a major source of autoantibody production, and activation of B cells via CD1 may play an important role in the pathogenesis of lupus.
Zeng
D
D
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94306, USA.
Lee
M K
MK
Tung
J
J
Brendolan
A
A
Strober
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D008181:Lupus Nephritis / Q000209:etiology* / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D001323:Autoantibodies; D007075:Immunoglobulin M