PubMed1976
The fragments related to the Cgamma2 and Cgamma3 homology regions of human IgG, described in the preceding paper by Ellerson, et al. were assayed for their ability to interact with complement, engage in cytophilic activity toward macrophages, and to play a role in controlling the catabolism of the whole IgG. The Cgamma2-fragment retained about 3% of the activity of intact IgG in a whole complement-fixing assay in which the test proteins were absorbed as mono-layers onto polystyrene latex beads. However, in a fluid-phase C1-binding assay this fragment showed the same activity as IgG and Fc fragment, when compared on a molar basis. Since the Cgamma2-fragment represented only one intact domain, full expression of complement-fixing activity appeared to be independent of quaternary interactions. Thus IgG possesses two C1-binding sites. The Cgamma3-fragment was inactive in both of the complement assays. The ability of IgG to interact with the Fc-receptor on guinea-pig macrophages was shown to be entirely a function of the Cgamma3 region. This was demonstrated both in a direct assay in which tanned red cells coated with Cgamma3-fragment formed rosettes with macrophages and in an indirect assay in which this fragment was able to inhibit rosette formation between IgG-coated red cells and macrophages. The rate of clearance of radiolabeled Cgamma2-, Cgamma3-, Fab, Fc fragments, and IgG from the circulation was measured in rabbits. The Cgamma2 fragment was cleared with a half-time similar to that shown by intact IgG and Fc (about 70 hr) whereas Cgamma3- and Fab fragments were cleared more rapidly (half-time, about 15 hr). The rate of cleaance was not related to the presence of sialic acid or exposed galactosyl residues at the termini of the carbohydrate prosthetic groups. These data clearly show that at least three of the biologic functions of IgG are mediated fully and independently by one or other of the Fc domains.