Bystander Help in Primary Immune Responses in Vivo

We evaluated the requirement for hapten-carrier linkage in the primary, T cell-dependent antibody response in vivo. Mice immunized with mixtures containing nonimmunogenic and immunogenic proteins developed antibody that was specific for determinants present on the nonimmunogenic carrier. Therefore, hapten-carrier linkage was not necessary for the generation of primary antibody responses. The magnitude of the bystander response was a function of the immunogenicity of the coimmunogen and the quantity of determinant-specific B cells available for activation. Interestingly, the kinetics of the bystander response, in contrast to the cognate response, were not accelerated in the presence of primed Th cells. Adoptive recipients reconstituted with primed Th cells developed accelerated cognate but not bystander antibody response, as compared with unprimed recipients. This phenomenon may reflect a regulatory mechanism invoked to limit the potentially harmful effects of nonspecific help. It was observed that while animals are tolerant to immunization with mouse (self) hemoglobin, immunization with a mixture containing mouse hemoglobin plus fowl gamma globulin resulted in the production of hemoglobin-binding autoantibodies. Thus bystander help induced by coimmunization may serve as a model for the induction of autoantibodies during normal immune responses in vivo.