Studies of the binding of monomeric murine IgG2a and IgG2b to the macrophage-like cell line P388D1 confirmed the existence of at least two classes of Fc receptors. One receptor binds IgG2a preferentially, whereas the second interacts better with IgG2b. Approximately equal numbers of each class of receptor were present. The receptors showed a marked cross-specificity toward IgG2 subclass proteins but did not recognize murine IgG1. The P388D1 receptors were used to study the phylogenetic emergence, the conservation, and evolution of the molecular structures necessary for the expression of cytophilic activity by IgG. Heterocytophilic activity of plasma, sera, or purified immunoglobulins from modern representatives of the major phylogenetic families was assessed by competitive displacement of specifically bound radiolabeled IgG2a or IgG2b. The P388D1 Fc receptors showed marked species specificity. Fish IgM and non-IgM 7S immunoglobulins from amphibians, reptiles, and avians lacked cytophilic activity toward P388D1; only turtle plasma could displace murine IgG2 proteins from their receptors. In higher vertebrate species, rat, rabbit, and human IgG competed for the two classes of receptor equally well. In contrast, both guinea pig IgG1 and IgG2, and also IgG from bovine, sheep, goat, horse, and opossum lacked the ability to interact with P388D1. Canine IgG could displace murine IgG2a but not IgG2b from their receptors. These results, when compared to the data available on macrophage receptors for homologous and heterologous IgG in most of the above species, indicate that cytophilic structures have diverged in parallel with the cell-surface receptors and that mouse, rabbit, and human macrophage Fc receptors are structurally related.
This work was supported by Grant MT 4259 from the Medical Research Council of Canada.