The role of non-immune IgG in controlling IgG-mediated effector functions.
The majority of evidence supports the conclusion that IgG-dependent effectors respond to antibodies which have been polymerized artificially or by polyvalent antigens, but not to monomeric IgG antibodies. Effectors can distinguish polymerized IgG antibodies from monomeric IgG because they contain multiple receptor units and can interact multivalently with polymerized IgG. However, monomeric IgG is present at very high concns in plasma and interstitial fluids and will inhibit multivalent interactions in vivo between polymerized antibody and effectors. Such inhibition raises the question of how IgG-mediated effector responses could function in vivo. In this review we present a mathematical model which quantitatively predicts how polyvalent ligands interact multivalently with receptors in the presence of excess monovalent ligand. We then show that results from experiments in vitro using such diverse systems as the binding and endocytosis of immune complexes by macrophages, complement-mediated lysis of antibody-coated target cells, and ADCC can be explained qualitatively by the model. We conclude that monomeric IgG does not totally inhibit IgG-mediated effector functions but, rather, raises the threshold of antibody binding which is required to elicit a response. We then consider how non-immune IgG may serve as a homeostatic regulator of IgG-dependent responses, in vivo, perhaps for the purpose of inhibiting responses to low levels of cell-bound IgG autoantibodies.
D000328:Adult; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001704:Biopolymers; D003166:Complement Activating Enzymes / Q000276:immunology; D003167:Complement Activation; D015922:Complement C1q; D004136:Dinitrobenzenes / Q000276:immunology; D004705:Endocytosis; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D008024:Ligands; D008954:Models, Biological; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001704:Biopolymers; D004136:Dinitrobenzenes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008024:Ligands; D011961:Receptors, Fc; D017452:Receptors, IgG; D015922:Complement C1q; D003166:Complement Activating Enzymes