The effects of immunoglobulin isotype and antibody affinity on complement-mediated inhibition of immune precipitation and solubilization.
We have studied complement-mediated prevention of precipitation (PIP) and solubilization of immune complexes (IC) formed with DNP19-BSA and murine monoclonal antibodies (MCAs) of different isotypes and affinities. PIP was effective for IC formed with IgG1 and IgM antibodies, but not for IgA MCA. For IgG1 MCAs, affinity appeared to exert a minor effect on PIP, and IC formed in antibody excess or at equivalence were retained in solution more readily than those formed in antigen excess. For IgM MCAs affinity and antigen-antibody ratio did not affect PIP. As PIP did not occur in Mg-EGTA, it was concluded that PIP was entirely classical pathway dependent. Solubilization of IC containing IgG1 MCAs occurred more rapidly and to a greater extent with low affinity antibodies and an inverse relationship between affinity and the extent of solubilization was observed. Complexes formed with IgG1 MCAs were solubilized relatively poorly when formed in antigen excess. In contrast, affinity and antigen-antibody ratio did not influence the rate and extent of solubilization of IC containing IgM MCAs. IC formed with IgG2b were solubilized rapidly whereas those formed with IgG2a or IgA were solubilized poorly. The relative contributions of the classical and the alternative pathways to solubilization varied with each antibody and the effect of antigen-antibody ratio on these relative contributions was inconsistent.
University Department of Pathology, Western Infirmary, Glasgow, U.K.
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Johnson
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Harkin
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Steward
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Whaley
D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D011232:Chemical Precipitation; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000276:immunology*; D004140:Dinitrophenols / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D007700:Kinetics; D012710:Serum Albumin, Bovine / Q000276:immunology; D012995:Solubility
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D004140:Dinitrophenols; D007132:Immunoglobulin Isotypes; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D003165:Complement System Proteins