The specificity of in vivo tolerance to haptens in NZB and normal mice after exposure to hapten-modified syngeneic spleen cells

Abstract

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.