Fc-Dependent IgG-Mediated Suppression of the Antibody Response: Fact or Artefact?

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Abstract
IgG antibodies have been shown to suppress the antibody response to all epitopes of their specific antigen as well as those the IgG do not bind to, so-called ‘non-epitope-specific suppression‘. The present study was undertaken to clarify whether there is a true IgG-mediated Fc-dependent suppression of Ihe antibody response. This question is of fundamental importance to the understanding of the mechanism behind this phenomenon. It is demonstrated that F(ab')2 fragments of a monoclonal TNP (trinitrophenyl)-specific IgG2a antibody are unable to suppress the murine in vitro non-epitope-specific plaque-forming cell response against SRBC (sheep erythrocytes) when SRBC-TNP is used as antigen. The same monoclonal IgG aniibody. when administered in intact form, is able lo induce up to 98% suppression of the SRBC-specific antibody response. The lack of suppression is not due to mitogenic effects of pepsin in the F(ab')2 fractions or increased breakdown of F(ab'); fragments, as compared with intact antibody, in the cultures. These data clearly demonstrate that there is indeed a highly efficient, Fc-dependent, nonepitope-specific suppressive mechanism mediated by IgG aniibodies and support a hypothesis involving binding of the anligcn-anlibody complexes lo Fc receptors as a step in the effector mechanism.