The i.p. injection of both hyperimmune antibody to leukemia L1210 and soluble antigen derived from L1210, sequentially or as soluble immune complexes, suppressed receptors for cytophilic antibody on macrophages of allogeneic mice. This phenomenon has been shown previously to be thymus dependent. The suppressed peritoneal macrophages were small and lacked the morphological appearance characteristic of activated macrophages, which were elicited by immunization with intact L1210 cells alone. Suppressed macrophages were unable to attach L1210 cells in the presence of specific cytophilic antibody. Maximum suppression was observed 8 to 10 days after treatment with immune complexes. Only immune complexes containing immunoglobulin G antibody produced inhibition of macrophages; immunoglobulin M-containing complexes did not. Inhibition was immunologically specific in that macrophages unable to attach cytophilic antibody to L1210 could fix antibody to an unrelated leukemia, EL4. Conversely, macrophages inhibited by the administration of EL4-containing immune complexes were able to attach antibody to L1210. Soluble antigen alone produced neither inhibition nor activation of macrophages and did not prevent the activation of macrophages by a subsequent injection of intact L1210 cells. The Fc portion of immunoglobulin was required for the suppressive effects of immune complexes. Even high doses of immune complexes containing F(ab′)2 from immunoglobulin G antibody were ineffective in producing suppression in vivo. Likewise, Fc fragments alone had no effect. We conclude that immune complexes specifically impair the arming of macrophages by cytophilic antibody and that the Fc portion of antibody is essential for this effect.
Supported by American Cancer Society Grant IM 50B (Laurens Hammond Memorial Grant for Cancer Research) and USPHS Grant CA 13105. Presented in part at the 68th Annual Meeting of the American Association for Cancer Research (33).