Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1985 Sep 1;162(3):877–889. doi: 10.1084/jem.162.3.877

IgG bearing covalently bound C3b has enhanced bactericidal activity for Escherichia coli 0111

PMCID: PMC2187805  PMID: 3897448

Abstract

The mechanism was sought by which bactericidal IgG for E. coli 0111 (strain 12015) increases the bactericidal efficiency of C5b-9. IgG did not affect the distribution of C3 deposition on the O-Ag capsule and the outer membrane of 12015, suggesting that bactericidal IgG was not directing complement activation to different sites on the bacterial surface. However, one-fifth of the C3 that was deposited in the presence of IgG attached covalently to the antibody molecule. Covalent complexes between purified C3b and IgG were prepared in order to study the role of C3b-IgG in the bactericidal reaction. 8-10-fold less C3b- IgG than IgG was necessary to sensitize 12015 for serum killing. When aggregates were eliminated from the C3b-IgG and IgG preparations by sucrose density gradient ultracentrifugation, C3b-IgG remained three- to fourfold more effective than IgG on a molecule-for-molecule bound basis in mediating the serum bactericidal reaction. These results suggest that formation of C3b-IgG during the serum bactericidal reaction is critical for killing, and have important implications for the development of effective bactericidal vaccines.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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 T. A., Cole R. M., Chused T. M., Hammer C. H., Frank M. M. Biotinylation of human C3. Mol Immunol. 1982 Jul;19(7):857–864. doi: 10.1016/0161-5890(82)90351-0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Daha M. R., Fearon D. T., Austen K. F. C3 requirements for formation of alternative pathway C5 convertase. J Immunol. 1976 Aug;117(2):630–634. [PubMed] [Google Scholar]
  5. Fries L. F., Gaither T. A., Hammer C. H., Frank M. M. C3b covalently bound to IgG demonstrates a reduced rate of inactivation by factors H and I. J Exp Med. 1984 Dec 1;160(6):1640–1655. doi: 10.1084/jem.160.6.1640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Goldman R. C., White D., Orskov F., Orskov I., Rick P. D., Lewis M. S., Bhattacharjee A. K., Leive L. A surface polysaccharide of Escherichia coli O111 contains O-antigen and inhibits agglutination of cells by O-antiserum. J Bacteriol. 1982 Sep;151(3):1210–1221. doi: 10.1128/jb.151.3.1210-1221.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Hill A. W., Shears A. L., Hibbitt K. G. The requirement of specific antibody for the killing of E. coli by the alternate complement pathway in bovine serum. Immunology. 1978 Jan;34(1):131–136. [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Joiner K. A., Goldman R. C., Hammer C. H., Leive L., Frank M. M. Studies of the mechanism of bacterial resistance to complement-mediated killing. V. IgG and F(ab')2 mediate killing of E. coli 0111B4 by the alternative complement pathway without increasing C5b-9 deposition. J Immunol. 1983 Nov;131(5):2563–2569. [PubMed] [Google Scholar]
  12. 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]
  13. Joiner K. A., Goldman R., Schmetz M., Berger M., Hammer C. H., Frank M. M., Leive L. A quantitative analysis of C3 binding to O-antigen capsule, lipopolysaccharide, and outer membrane protein of E. coli 0111B4. J Immunol. 1984 Jan;132(1):369–375. [PubMed] [Google Scholar]
  14. Joiner K. A., Hammer C. H., Brown E. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of Salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane. J Exp Med. 1982 Mar 1;155(3):809–819. doi: 10.1084/jem.155.3.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Joiner K. A., Schmetz M. A., Goldman R. C., Leive L., Frank M. M. Mechanism of bacterial resistance to complement-mediated killing: inserted C5b-9 correlates with killing for Escherichia coli O111B4 varying in O-antigen capsule and O-polysaccharide coverage of lipid A core oligosaccharide. Infect Immun. 1984 Jul;45(1):113–117. doi: 10.1128/iai.45.1.113-117.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Medicus R. G., Götze O., Müller-Eberhard H. J. Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway. J Exp Med. 1976 Oct 1;144(4):1076–1093. doi: 10.1084/jem.144.4.1076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Schenkein H. A., Ruddy S. The role of immunoglobulins in alternative pathway activation by zymosan. II. The effect of IgG on the kinetics of the alternative pathway. J Immunol. 1981 Jan;126(1):11–15. [PubMed] [Google Scholar]
  20. Steele E. J., Rowley D. The mechanism of complement fixation by rabbit F(ab')2: properties of the bactericidal reaction. Immunochemistry. 1977 May;14(5):319–324. doi: 10.1016/0019-2791(77)90230-0. [DOI] [PubMed] [Google Scholar]
  21. Steele N. P., Munson R. S., Jr, Granoff D. M., Cummins J. E., Levine R. P. Antibody-dependent alternative pathway killing of Haemophilus influenzae type b. Infect Immun. 1984 May;44(2):452–458. doi: 10.1128/iai.44.2.452-458.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Tarr P. I., Hosea S. W., Brown E. J., Schneerson R., Sutton A., Frank M. M. The requirement of specific anticapsular IgG for killing of Haemophilus influenzae by the alternative pathway of complement activation. J Immunol. 1982 Apr;128(4):1772–1775. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES