Cellular Changes and Gamma Globulin Production in Mouse Spleen during Induction of Immunological Tolerance

Abstract

In recent years it has been found in different experimental systems that an increase in the immunizing dose of antigen above a certain threshold leads, somewhat paradoxically, to a gradual decrease in the subsequent immune reaction (see review by Iványi and Cerný [1]). It was possible to produce a high concentration of soluble protein antigen which did not induce specific differentiation of antibody-forming cells, but led directly to the inhibition of their function. Evidence at the cellular level was provided directly in vivo, in chickens, by following the antibody-forming cells (antihuman serum albumin) with the immunofluorescence method [2], and by inducing the primary immune responsein vitro with a special technique that demonstrated cells forming antibodies against bacterial antigen [3]. In control experiments arranged in a way similar to both cases mentioned above, the authors excluded the possibility that the absence of antibody-forming cells after stimulation with a high concentration of antigen might be due to “masking” (neutralization) of antibodies in cells with an excess of antigenic determinants. Recently, in experiments on the continuation of immune reaction in tissue fragments in vitro, Iványi et al. [4] found that a high concentration of antigen (HSA) inhibited not only the synthesis of antibodies but also probably the formation of specific Actinomycin-D-sensitive RNA.