The role of B cells in lpr/lpr-induced autoimmunity.
The primary roles of T cells and B cells in the initiation of systemic autoimmunity are unclear. To investigate the role of B cells, we crossed the "Jh knockout" mutation onto the autoimmune lpr/lpr background. Animals homozygous for both traits were obtained. As expected, these animals lack B cells. These animals also show no signs of autoimmune kidney destruction nor vasculitis, in spite of carrying the lpr/lpr mutation. In contrast, lpr/lpr littermates that had B cells had severe nephritis and vasculitis, as well as autoantibodies. These results demonstrate a primary role for B cells and/or (auto)antibodies in initiating several types of autoimmune-mediated tissue destruction. The implications of this finding for models and therapy of autoimmunity are discussed.
Shlomchik
M J
MJ
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Madaio
M P
MP
Ni
D
D
Trounstein
M
M
Huszar
D
D
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology*; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D008181:Lupus Nephritis / Q000209:etiology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D014657:Vasculitis / Q000209:etiology
D001323:Autoantibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens