Modulation of Fc receptors of mononuclear phagocytes by immobilized antigen-antibody complexes. Quantitative analysis of the relationship between ligand number and Fc receptor response.
Macrophages plated on surfaces coated with antigen-IgG complexes lose the capacity to bind and ingest IgG-coated particles via their Fc receptors (FcR). Macrophages plated on surfaces containing a similar number of IgG molecules that are not complexed to antigen show little or no decrease in FcR activity. Using a rat monoclonal antibody (2.4G2 IgG) directed against the trypsin-resistant FcR (FcRII) of mouse macrophages we show that the decrease in receptor activity induced by substrate-adherent immune complexes is caused by the physical removal of 60 and 75% of FcRII from the nonadherent membrane surfaces of resident and thioglycollate broth-induced macrophages, respectively. Macrophages maintained on antigen-IgG-coated surfaces for up to 44 h show no recovery in FcRII activity or number, while macrophages on control surfaces exhibit two and threefold increases, respectively, in these parameters. Macrophages maintained for 72 h on antigen-IgG-coated surfaces show a small recovery in FcRII activity, and in the number of FcRII that is accessible to bind 125I-2.4G2 IgG. FcRII modulation, as measured by the binding of 125I-labeled 2.4G2 IgG, is initiated when the number of IgG molecules bound to the substrate is approximately equal to the total number of FcRII on the plasma membranes of all the macrophages on the substrate. FcRII activity and number decrease linearly as the number of substrate-bound IgG molecules increases exponentially, and are maximally reduced when the number of IgG molecules on the substrate is 20-fold greater than the total number of all FcRII on the surfaces of all the macrophages in the culture. Thus there is a stoichiometric relationship between the number of IgG molecules on the substrate and the extent of FcRII modulation.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D004136:Dinitrobenzenes / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010587:Phagocytosis; D011961:Receptors, Fc / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D004136:Dinitrobenzenes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc