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. 1971 Mar 31;133(4):713–739. doi: 10.1084/jem.133.4.713

STUDIES ON ANTIGEN-ANTIBODY COMPLEXES

I. ELIMINATION OF SOLUBLE COMPLEXES FROM RABBIT CIRCULATION

Mart Mannik 1, William P Arend 1, Anthony P Hall 1, Bruce C Gilliland 1
PMCID: PMC2138971  PMID: 5547056

Abstract

Solid phase immunoadsorbents were prepared by coupling antigens to agarose. With this technique specific antibodies were easily isolated in large amounts. The γG-globulin class of antibodies isolated in this manner were not denatured as judged by their normal biological half-life in rabbits. Soluble immune complexes at fivefold antigen excess were prepared from isolated specific antibodies and HSA, human λ-chains, human λG-globulins, and a Waldenström's macroglobulin as antigens. In all these preparations a characteristic immune complex was encountered that represented the smallest stable antigen-antibody union. In the HSA-anti-HSA system they were found to be AgAb2 complexes, and Ag2Ab complexes in the γG-anti-γG system. These stable complexes fixed complement ineffectively. Also, a spectrum of larger complexes was present in each system, and these complexes fixed complement effectively. With intact antibodies the disappearance curves of immune complexes from the circulation were composed of three exponential components. The immune complexes larger than AgAb2 were quickly removed from the circulation with half-lives of 0.09–0.37 hr. Their clearance was not dependent on complement components, in that depletion of complement by cobra venom factor and aggregated γG-globulin did not alter the pattern of their removal from the circulation. However, when the interchain disulfide bonds of antibodies were reduced and alkylated, the removal of the λ-anti-λ, HSA-anti-HSA, and γG-anti-γG complexes was altered. In these experiments the disappearance curves were composed of two exponential components and the rapid removal of the greater than AgAb2 complexes did not occur. The immune complexes prepared from reduced and alkylated antibodies fixed complement ineffectively. The presented data indicate that the rapid removal of circulating immune complexes, containing γG-globulin molecules as antibodies, depends primarily on the number of antibodies involved. Furthermore, complement fixation is not involved in the rapid removal of such complexes. Nevertheless, the rapid removal of immune complexes and their ability to fix complement have similarities for optimal function in that both processes require intact interchain disulfide bonds of antibodies and complexes that exceed the AgAb2 combination.

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Selected References

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