Regulation of the immune response. V. An analysis of the function of the Fc portion of antibody in suppression of an immune response with respect to interaction with components of the lymphoid system

Abstract

Pepsin digested, F(ab')₂ antibody has less ability to inhibit an antibody response than has intact IgG antibody, when the antibodies were given one day after antigen. F(ab')₂ antibody has to be given with antigen to attain maximal suppression, while IgG antibody, administered after antigen, is still highly immunosuppressive. The IgG antibody was able to terminate established immune responses, whereas F(ab')₂ antibody could not do so. We interpret these findings to indicate that F(ab')₂ antibody suppresses immune responses by simple masking of antigen, whereas IgG antibody alters the immune response through a further activity which takes place after antibody has combined with antigen. This further activity involves the Fc portion of antibody. Two alterations in immune mechanism are suggested: (1) increased destruction of antigen and (2) inactivation of the antibody forming cell precursor population by antigen—antibody complexes. This latter possibility is considered in detail. The tripartite inactivation model has been constructed to explain the presently known observations concerning immunosuppression by antibody and to make a prediction which has been verified. A further prediction concerning the affinities of antibodies produced under IgG or F(ab')₂ antibody-mediated immunosuppression is put forward.

Thymus-bone marrow cell synergism does not give a simple thymus cell dose-response relationship but a multi-phasic relationship where the response increases once the dose of thymus cells is decreased to a sufficiently low level. Such a dose-response relationship is not explainable in terms of the usual mechanisms proposed for thymus-bone marrow cell interaction and this deviation from a simple dose-response relationship is interpreted in terms of the proposed function of thymus-derived cells in controlling antibody feedback regulation.