Granulocyte fcγ receptor recognition of cell bound and aggregated IgG: Effect of γ‐interferon

Granulocyte Fcγ receptors are important components in the recognition of IgG‐coated cells and immune complexes. Two proteins have been identified on resting human granulocytes which function as Fcγ receptors, Fcγ RII (CD32) and Fcγ RIII (CD16). A third protein, Fcγ RI (CD64), is not constitutively expressed on resting granulocytes, but can be induced by activation with γ‐interferon. We examined the role of these three Fcγ receptors on human granulocytes in the binding of both IgG‐sensitized erythrocytes and soluble oligomeric IgG. In these studies we employed anti‐Fcγ receptor antibodies which complete for the Fcγ RII and Fcγ RIII ligand binding sites. Preincubation of granulocytes with saturating concentrations of high‐affinity anti‐Fcγ RII monoclonal antibody did not alter the recognition of IgG sensitized human cells by granulocytes. Furthermore, ligand binding studies demonstrated that anti‐Fcγ RII antibody altered neither the number nor the affinity of granulocyte binding sites for human trimeric IgG. In contrast, Fab anti‐Fcγ RIII inhibited the binding of both IgG (anti‐D) sensitized human RBCs and IgG sensitized sheep RBCs. Similarly, a reduction in the expression of Fcγ RIII by treatment with phosphatidyl‐inositol specific phospholipase C reduced PMN recognition of IgG‐sensitized cells. Also, anti‐Fcγ RIII decreased the number of granulocyte binding sites for human IgG trimer without a change in receptor affinity. Fcγ RI, which was induced by γ‐IFN, increased granulocyte recognition of both IgG sensitized RBCs and IgG trimer. These data suggest that Fcγ RIII is the primary Fcγ receptor on granulocytes which recognizes IgG sensitized RBCs and low molecular weight complexes of IgG. With γ‐interferon activated granulocytes, Fcγ RI appears to enhance this recognition process.