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Role of Antibody and Complement in the Immune Clearance and Destruction of Erythrocytes II. MOLECULAR NATURE OF IgG AND IgM COMPLEMENT-FIXING SITES AND EFFECTS OF THEIR INTERACTION WITH SERUM

作者:Alan D. Schreiber, Michael M. Frank · 发表于:Journal of Clinical Investigation · 年份:1972 · DOI:10.1172/jci106847 · 被引用次数:122 · 研究领域:Erythrocyte Function and Pathophysiology、Immune Cell Function and Interaction、Chemical and Physical Studies

A model for the immune clearance and destruction of homologous erythrocytes has been further explored. In this model, every IgM anti-erythrocyte antibody molecule in an antibody preparation was shown to fix Cl. About 2000 IgG antibody molecules were required to form a Cl-fixing site on the guinea pig erythrocyte surface. 60 IgM complement-fixing sites per erythrocyte were required for the immune clearance of IgM-sensitized erythrocytes. This number of sites could be detected by a direct agglutination test. 1.4 complement-fixing sites were required for immune clearance of IgG-sensitized cells, a number of molecules which could not be detected by direct agglutination. This number could, however, be detected with the use of a Coombs antiglobulin reagent. Depletion of the late components of complement (C3-9) with cobra venom was associated with the loss of ability to clear IgM-sensitized cells and a marked deficit in the ability to clear IgG-coated cells. Thus, late (C3-9) components of complement as well as an early component (C4) were required for normal clearance of sensitized erythrocytes. There was no evidence that activation of the alternate pathway of complement action could lead to accelerated erythrocyte clearance. In vitro incubation of IgG and IgM-sensitized erythrocytes in fresh serum led to deposition of C3 and C4 on the erythrocyte surface. IgM-sensitized cells treated in this way had a normal survival. IgM-sensitized cells also were shown to remain Coombs positive ...