Immunoglobulin-mediated shifting of immune complexes to increased complement-dependent solubility and immunoadherence.
The effect of a monomeric polyclonal polyspecific IgG preparation (mIgG) for i.v. use on the capacity of fresh normal human serum (NHS) to inhibit precipitation of immune complexes of tracer-labeled bovine serum albumin (BSA) and anti-BSA (aBSA) rabbit antibody was investigated. Relative to heat-inactivated serum which showed no capacity to inhibit immune complex precipitation (CIICP), fresh NHS at a final dilution of 1:3 or 1:2 showed a 12 and 46% CIICP, respectively, with a BSA:aBSA ratio at equivalence. Addition of incremental amounts of mIgG dose-dependently enhanced CIICP of NHS to reach 63 and 90%, respectively, at a concn of 13.0 mg/ml mIgG. Human serum albumin instead of mIgG had no influence on CIICP of NHS indicating that the phenomenon was not dependent on non-specific protein-protein interactions. Although minimal amounts of BSA cross-reactivity could be demonstrated in mIgG, the extent of this activity was too small to explain the CIICP-supporting effect of mIgG as determined by comparing the effect of mIgG and aBSA serum on CIICP of fresh serum. Furthermore, absorption of mIgG on BSA-Sepharose did not lead to impairment of its CIICP-supporting effect. A direct binding of tritium-labeled mIgG (3H-mIgG) to either insoluble BSA:aBSA complexes or latex-bound IgG (IgG-latex) was found. Incubation of 2.7 micrograms 3H-mIgG with 90 micrograms IgG-latex resulted in a specific binding of 5.2% of the labeled compound. Such binding could be inhibited by unlabeled mIgG. Binding of mIgG was mediated through the Fab as well as the Fc part of the molecules: the 3H-Fc as well as the 3H-Fab fragment of mIgG bound to IgG-latex. The extent of binding of Fc was more than twice that of Fab and amounted to 70-90% of the binding found with intact mIgG. In an immune adherence hemagglutination system that depends on the interaction of complement-reacted immune complexes with C3b receptor-bearing erythrocytes, evidence was obtained that the mIgG preparation facilitated fixation of C3b to performed BSA:aBSA complexes. Addition of 1.45 mg/ml mIgG reduced the quantity of antigen-complexed C3b-bearing aBSA antibodies required to show a given agglutination by a factor of 3-4. We conclude that the facilitating effect of high doses of mIgG on complement-dependent CIICP of NHS and on immune adherence hemagglutination is the amplifying effect of complement after an initial interaction of antigen-nonspecific polyclonal polyspecific IgG with antigen-reacted antibody.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002417:Cattle; D003179:Complement C3b / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D006386:Hemagglutination Tests; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D016756:Immunoglobulins, Intravenous
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D003179:Complement C3b; D003165:Complement System Proteins