Fc-dependent monoclonal IgG1-mediated suppression of antibody response

It has been known for a long time that passively administered antibodies (Abs) or immune complexes regulate the immune response to their specific antigen (Ag). IgG may sometimes suppress the humoral immune response against soluble antigens. The exact mechanism behind this phenomenon has not been understood yet and the requirement for the Fc part is still a matter of controversy. The present study was undertaken to clarify whether there is a true IgG-mediated Fc-dependent suppression of the immune response. Antigen and monoclonal antibody (mAb) used in this study were recombinant human interferon gamma (r-hIFN-gamma) and mouse monoclonal antibodies specific for human IFN-gamma [anti-hIFN-gamma mAb (CAy-IFNgamma38)] respectively. An intact IgG-free preparation of Fab plus various Fc fragments was prepared from papain-digested CAy-IFNgamma38. Ag/IgG and Ag/Fab complexes were prepared at various molar ratios. Keeping the Ag doses constant, mice were immunized either with Ag, Ag/IgG or Ag/Fab complexes. Primary immunization and the boosting were performed with the samples in complete and incomplete Freund's adjuvants respectively. Specific antibody levels were measured by an ELISA. Immunization performed with Ag/Fab complexes even at a molar ratio of 1:1.36 did not result in marked suppression of the response when compared to that of Ag only-immunization. In contrast, Ag/IgG complexes resulted in nearly 90% suppression of the antibody response. Our observations suggest that Fc part of IgG molecule plays a crucial role in suppression of the in vivo antibody response against the Ag when complexed with intact IgG.