Diseases caused by reactions of T lymphocytes to incompatible structures of the major histocompatibility complex. V. High titers of IgG autoantibodies to double-stranded DNA.
IgG autoantibodies to double-stranded DNA (dsDNA), reaching a maximal serum titer of 1 in 2560, were spontaneously produced by (C57BL/10 x DBA/2)F1 mice injected with T lymphocytes from strain DBA/2. Anti-dsDNA antibodies were detected by the indirect immunofluorescence technique applying the kinetoplast dsDNA of Crithidea luciliae as antigenic substrate. The anti-dsDNA antibodies belonged to the IgG1, IgG2, IgM, and IgA (sub)classes. That of least some of them were produced by B cells of the F1 recipients was shown by the presence of F1-derived Ig-1b allotypic markers on such antibodies. In the F1 recipients, an incompatibility at H-2 was required for the formation of anti-dsDNA. These findings are consistent with the concept that the mechanism underlying the formation of SLE-like autoantibodies in this model is an abnormal cooperation between alloreactive donor T cells, presumably helper T (TH) cells, and H-2-incompatible F1 B cells. It is known from the literature that abnormal T-B cell cooperation is a unique tool for inducing vigorous primary antibody responses to antigens that carry repeating antigenic determinants on a rigid backbone and are poor immunogens or tolerogens in the absence of abnormal T-B cell cooperation. We suggest that the self-antigen dsDNA falls into the same category of structurally and immunologically peculiar antigens.
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D004247:DNA / Q000276:immunology; D005260:Female; D006087:Graft vs Host Reaction; D006183:H-2 Antigens; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007136:Immunoglobulins / Q000145:classification; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D006183:H-2 Antigens; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007136:Immunoglobulins; D004247:DNA