The specificity of in vivo tolerance to haptens in NZB and normal mice after exposure to hapten-modified syngeneic spleen cells.
We have evaluated hapten-specific hyporesponsiveness induced by in vivo administration of TNP-modified syngeneic spleen cells (TNP-SC). Pretreatment of non-autoimmune mice led to hyporesponsiveness to challenge with either TNP or the closely related hapten DNP coupled to Ficoll. There was also a significant reduction of the direct PFC response after challenge with TNP-HGG. In tolerized mice challenged with TNP-HGG, the IgM portion of the serum response was similarly suppressed; however, the total serum antibody as well as the indirect PFC response was not suppressed. There was no tolerance at all when the mice were challenged with DNP-HGG. Thus, exposure to TNP-SC results in an incomplete form of hapten-specific B cell tolerance. This tolerance is selective for the IgM isotype and does not extend to the cross-reactive hapten DNP on a thymic-dependent carrier, although it does extend to a DNP on a thymic-independent carrier. Autoimmune NZB mice were defective with regard to tolerance after injection of hapten-modified syngeneic spleen cells. They did manifest a reduced direct PFC response to the challenge with TNP-Ficoll, but failed to demonstrate cross-tolerance to DNP-Ficoll challenge. Moreover, they did not have suppression of the hapten-specific IgM response after challenge with TNP on the thymic-dependent carrier. These abnormalities in tolerance induction in NZB mice to modified self may help to explain the loss of self-tolerance that occurs spontaneously and is expressed as autoimmune disease.
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage; D004136:Dinitrobenzenes / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000096:biosynthesis; D017710:Lymphocyte Transfusion; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology; D005719:gamma-Globulins / Q000276:immunology
D000941:Antigens; D004136:Dinitrobenzenes; D006241:Haptens; D007075:Immunoglobulin M; D014301:Trinitrobenzenes; D005719:gamma-Globulins