Fc-dependent IgG-mediated suppression of the antibody response: fact or artefact?

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 the 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 antibody, when administered in intact form, is able to 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')2 fragments, as compared with intact antibody, in the cultures. These data clearly demonstrate that there is indeed a highly efficient, Fc-dependent, non-epitope-specific suppressive mechanism mediated by IgG antibodies and support a hypothesis involving binding of the antigen-antibody complexes to Fc receptors as a step in the effector mechanism.