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. 1984 Dec 1;160(6):1640–1655. doi: 10.1084/jem.160.6.1640

C3b covalently bound to IgG demonstrates a reduced rate of inactivation by factors H and I

PMCID: PMC2187521  PMID: 6239898

Abstract

We have prepared C3b covalently linked to IgG via a hydroxylamine- sensitive bond between the C3b alpha' chain and sites predominantly, but not exclusively, located in the IgG heavy chain. This C3b species displays relative resistance to inactivation by factors H and I when compared with free C3b. This resistance appears to be due entirely to reduced affinity of C3b-IgG for factor H. Resistance to inactivation is not conferred on C3b by binding to another serum glycoprotein of similar size, ceruloplasmin, and may be a special property of IgG. C3b- IgG demonstrates an enhanced capacity to consume serum C3 relative to C3b. These alterations of the behavior of C3b when bound to IgG may in part explain the augmentation of alternative pathway activity by IgG. In addition, IgG-induced protection of C3b might influence both complement-mediated killing and phagocytosis of bacteria, as well as modify the in vivo handling of IgG-containing soluble immune complexes.

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Selected References

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  1. Arnaout M. A., Dana N., Melamed J., Medicus R., Colten H. R. Low ionic strength or chemical cross-linking of monomeric C3b increases its binding affinity to the human complement C3b receptor. Immunology. 1983 Feb;48(2):229–237. [PMC free article] [PubMed] [Google Scholar]
  2. Berger M., Gaither I. A., Frank M. M. Complement receptors. Clin Immunol Rev. 1981;1(4):471–545. [PubMed] [Google Scholar]
  3. Berger M., Gaither T. A., Hammer C. H., Frank M. M. Lack of binding of human C3, in its native state, to C3b receptors. J Immunol. 1981 Oct;127(4):1329–1334. [PubMed] [Google Scholar]
  4. Brown E. J., Berger M., Joiner K. A., Frank M. M. Classical complement pathway activation by antipneumococcal antibodies leads to covalent binding of C3b to antibody molecules. Infect Immun. 1983 Nov;42(2):594–598. doi: 10.1128/iai.42.2.594-598.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Capel P. J., Groeneboer O., Grosveld G., Pondman K. W. The binding of activated C3 to polysaccharides and immunoglobulins. J Immunol. 1978 Dec;121(6):2566–2572. [PubMed] [Google Scholar]
  6. Edwards M. S., Nicholson-Weller A., Baker C. J., Kasper D. L. The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus. J Exp Med. 1980 May 1;151(5):1275–1287. doi: 10.1084/jem.151.5.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fearon D. T. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med. 1980 Jul 1;152(1):20–30. doi: 10.1084/jem.152.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gadd K. J., Reid K. B. The binding of complement component C3 to antibody-antigen aggregates after activation of the alternative pathway in human serum. Biochem J. 1981 May 1;195(2):471–480. doi: 10.1042/bj1950471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gaither T. A., Hammer C. H., Frank M. M. Studies of the molecular mechanisms of C3b inactivation and a simplified assay of beta 1H and the C3b inactivator (C3bINA). J Immunol. 1979 Sep;123(3):1195–1204. [PubMed] [Google Scholar]
  10. Griffin F. M., Jr Roles of macrophage Fc and C3b receptors in phagocytosis of immunologically coated Cryptococcus neoformans. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3853–3857. doi: 10.1073/pnas.78.6.3853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hammer C. H., Wirtz G. H., Renfer L., Gresham H. D., Tack B. F. Large scale isolation of functionally active components of the human complement system. J Biol Chem. 1981 Apr 25;256(8):3995–4006. [PubMed] [Google Scholar]
  12. Harrison R. A., Lachmann P. J. The physiological breakdown of the third component of human complement. Mol Immunol. 1980 Jan;17(1):9–20. doi: 10.1016/0161-5890(80)90119-4. [DOI] [PubMed] [Google Scholar]
  13. Jacobs R. J., Reichlin M. Generation of low m.w., C3-bearing immunoglobulin in human serum. J Immunol. 1983 Jun;130(6):2775–2781. [PubMed] [Google Scholar]
  14. Joiner K. A., Goldman R. C., Hammer C. H., Leive L., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. VI. IgG increases the bactericidal efficiency of C5b-9 for E. coli 0111B4 by acting at a step before C5 cleavage. J Immunol. 1983 Nov;131(5):2570–2575. [PubMed] [Google Scholar]
  15. Kazatchkine M. D., Fearon D. T., Austen K. F. Human alternative complement pathway: membrane-associated sialic acid regulates the competition between B and beta1 H for cell-bound C3b. J Immunol. 1979 Jan;122(1):75–81. [PubMed] [Google Scholar]
  16. Kulics J., Rajnavölgyi E., Füst G., Gergely J. Interaction of C3 and C3b with immunoglobulin G. Mol Immunol. 1983 Aug;20(8):805–810. doi: 10.1016/0161-5890(83)90076-7. [DOI] [PubMed] [Google Scholar]
  17. Lawley T. J., Moutsopoulos H. M., Katz S. I., Theofilopoulos A. N., Chused T. M., Frank M. M. Demonstration of circulating immune complexes in Sjögren's syndrome. J Immunol. 1979 Sep;123(3):1382–1387. [PubMed] [Google Scholar]
  18. Medof M. E., Lam T., Prince G. M., Mold C. Requirement for human red blood cells in inactivation of C3b in immune complexes and enhancement of binding to spleen cells. J Immunol. 1983 Mar;130(3):1336–1340. [PubMed] [Google Scholar]
  19. Moore F. D., Jr, Austen K. F., Fearon D. T. Antibody restores human alternative complement pathway activation by mouse erythrocytes rendered functionally deficient by pretreatment with pronase. J Immunol. 1982 Mar;128(3):1302–1306. [PubMed] [Google Scholar]
  20. Moore F. D., Jr, Fearon D. T., Austen K. F. IgG on mouse erythrocytes augments activation of the human alternative complement pathway by enhancing deposition of C3b. J Immunol. 1981 May;126(5):1805–1809. [PubMed] [Google Scholar]
  21. Pangburn M. K., Müller-Eberhard H. J. Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. J Exp Med. 1980 Oct 1;152(4):1102–1114. doi: 10.1084/jem.152.4.1102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pangburn M. K., Schreiber R. D., Müller-Eberhard H. J. Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution. J Exp Med. 1977 Jul 1;146(1):257–270. doi: 10.1084/jem.146.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Polhill R. B., Jr, Newman S. L., Pruitt K. M., Johnston R. B., Jr Kinetic assessment of alternative complement pathway activity in a hemolytic system. II. Influence of antibody on alternative pathway activation. J Immunol. 1978 Jul;121(1):371–376. [PubMed] [Google Scholar]
  24. Schenkein H. A., Ruddy S. The role of immunoglobulins in alternative complement pathway activation by zymosan. I. Human IgG with specificity for Zymosan enhances alternative pathway activation by zymosan. J Immunol. 1981 Jan;126(1):7–10. [PubMed] [Google Scholar]
  25. Takata Y., Tamura N., Fujita T. Interaction of C3 with antigen-antibody complexes in the process of solubilization of immune precipitates. J Immunol. 1984 May;132(5):2531–2537. [PubMed] [Google Scholar]
  26. Venkatesh Y. P., Minich T. M., Law S. K., Levine R. P. Natural release of covalently bound C3b from cell surfaces and the study of this phenomenon in the fluid-phase system. J Immunol. 1984 Mar;132(3):1435–1439. [PubMed] [Google Scholar]

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