Scand. J. /mmunol. 29, 439^148. 1989 Dual Immunoregulatory Effects of Monoclonal IgG-Antibodies: Suppression and Enhancement of the Antibody Response E. J. WIERSMA, P. G. COULIE & B. HEYMAN Department of Immunology, Uppsala University. Biomedical Centre. Uppsala. Sweden, and Unit of Experimental Medicine, Universite Catholique de Louvain, Brussels, Belgium Wiersma. E,J. Coulie. P,G, & Heyman. B. Dual Immunoregulatory Etfects of Monoclonal IgG- AntibcxJies: Suppression and Enhancement of the Antibody Response, Scand. J. Immwwl. 29, 439-448. 19«9 Nine monoclonal IgG-anti-TNP antibodies were investigated for their ability to modulate anti- carrier responses in mice immunized with sheep red blood cells 2.4.6-tHnitrophenyl (SRBC- TNP) or keyhole limpet haemocyanin TNP (KLH-TNP). The antibodies enhanced the anti- carrier response when KLH TNP was used as antigen but suppressed it when SRBC TNP was used. The enhancing and suppressive efTects were not exerted by entirely the same sets of antibodies. The suppression was correlated to efficient antigen binding, but not complement activation, haemagglutination. or isolype of the monoclonal antibodies. In contrast, enhance- ment was correlated to isotypc and complement activation but not to antigen binding capacity. Both the enhancing and the suppressive effects seem to require Fc-mediated functions of the IgG molecules since they modulate the anti-carrier response although they recognize hapten determinants. Thus, one and the same monoclonal hapten-specific igG-antibody can enhance the anti-KLH response up to 38-fold whereas it suppresses the anti-SRBC response by more that 10-fold. E. J. Wiersma. Department of Immunology, BMC. Bo.\ 582, S-751 23 Uppsala, Sweden IgG antibodies can specifically suppress the humoral immune response against particulate as well as soluble antigens via a feedback mechanism 12. 10. 11. 16,41.42]. Often, more than 99':-i, of the immune response is suppressed. The mechanism behind this phenomenon is not yel understood, although it has been investigated since 1892 |I]. However, IgG antibodies may sometitnes en- hance instead of suppress both the primary [5. 8, 23] as well as the secondary [23. 24, 26] humoral immune response against soluble antigens. Most investigators have found that Fc com- pionents of the IgG molecule are crucial for the immunosupprcssive ability, F(ab'): fragments are at least 1000 times less efficient suppressors than intact IgG [39]. Monoclonal IgG antibodies, lacking carbohydrate chains due to their produc- tion in the presenee of a glycosylation inhibitor, bind antigen equally well as their glycosylated counterparts, but are deficient in Fc-reeeptor and complement binding [30] and also cannot induce immunosuppression [13]. Chicken IgG, which does not bind mammalian Fc receptors or fix mammalian complement, does not mediate immunosuppression [18. 22]. Finally, the finding that IgG antibodies with speeificity for one antigenic determinant on the antigen suppress the response against all epitopes in thai antigen [2. 3. 16. 22], also argues lor the importance of the Fc component. However, some authors have suggested that there are two different mechanisms by which IgG suppresses the humoral response. In addition to the Fc-dependent one mentioned above, an epi- tope-specific. Fc-independent mechanism is suggested, that acts at high concentrations ofIgG by blocking the antigenic determinants [19]. Other authors again suggested that in the physio- logical situation, the Fc-independent mechanism is the only relevant one [27]. The importance of efficient interaction between antigen and IgG for IgG-mediated suppression 439