Dimers of human immunoglobulin G1 provide an insufficient signal for their degradation by human monocytes.

In order to better define the processing of small soluble immune complexes by normal human monocytes, we have characterized the binding and degradation of human IgG1 monomers and covalently crosslinked dimers and heavier oligomers (composed predominantly of trimers, tetramers, and pentamers) by these cells. Whereas 15,000 molecules of monomeric IgG1 bound, about 110,000 and 65,000 IgG1 protomers of the oligomers and dimers, respectively, bound to the monocytes. Dimers bound dimerically to the cells as demonstrated by their enhanced rate of dissociation in the presence of excess heat-aggregated gamma-globulin. Despite occupying two Fc receptors, the intracellular fate of dimers was essentially that of the monomers; only 5-10% of the bound protomers were degraded. In contrast, approximately 40,000 IgG protomers of the heavy oligomers (30% of total bound) were degraded over a 5-hr incubation period. Since binding of a heavier complex, is required for degradation by the monocyte, dimeric immune complexes can generally escape the normal clearance mechanisms of the host.