Diseases caused by reactions of T lymphocytes towards incompatible structures of the major histocompatibility complex. VI. Autoantibodies characteristic of systemic lupus erythematosus induced by abnormal T-B cell cooperation across I-E.
By induction of a suitable graft-vs-host reaction (GVHR) in H-2-different F1 mice, one can induce the production of autoantibodies characteristic of systemic lupus erythematosus (SLE). The purpose of the present study was to define the intra-H-2 differences in the F1 recipients that are capable of triggering this process. A GVHR was induced in [B10.A(2R) x B10.A(4R)]F1 mice by injecting 10(8) lymphocytes from either parental strain. Whereas the donor B10.A(4R) induced a massive formation of autoantibodies to thymocytes, erythrocytes, nuclear antigens, and double-stranded DNA, the donor B10.A(2R) failed to do so. The intra-H-2 genetics of these two parent leads to F1 combinations are such that the observed autoantibody formation after the injection of B10.A(4R) T cells must have been triggered exclusively by the incompatible I-Ek subregion of the [B10.A(2R) x B10.A(4R)]F1 recipients. Because I-E appears to be the murine analogue of HLA-D/DR, this finding is of interest with respect to the increased frequency of certain HLA-DR alleles in SLE patients, as discussed.
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006087:Graft vs Host Reaction; D006649:Histocompatibility Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D008211:Lymphocyte Cooperation; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D004247:DNA