Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Feb;71(2):517–521. doi: 10.1073/pnas.71.2.517

The Molecular Basis of Self-Association of Antibodies to IgG (Rheumatoid Factors) in Rheumatoid Arthritis

Richard M Pope *, David C Teller †, Mart Mannik *
PMCID: PMC388038  PMID: 4131277

Abstract

The serum and synovial fluid of many patients with rheumatoid arthritis contain immune complexes composed of immunoglobulin G (IgG). In this study such complexes from one patient are shown to be formed by self-association of IgG-antibodies to IgG (IgG-rheumatoid factors), so that each molecule serves as an antibody as well as an antigen. All F(ab′)2 and Fab′ fragments derived from these complexes have antibody binding sites for normal IgG. Due to a high association constant in the formation of a cyclic complex by these antibodies, normal IgG is excluded as an antigen. These studies serve as a model for further elucidation of presence of similar immune complexes in the serum and synovial fluid of patients with rheumatoid arthritis.

Keywords: IgG-rheumatoid factor, ultracentrifugal analysis

Full text

PDF
517

Images in this article

520Image
on p.520

Selected References

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

  1. Arend W. P., Teller D. C., Mannik M. Molecular composition and sedimentation characteristics of soluble antigen-antibody complexes. Biochemistry. 1972 Oct 24;11(22):4063–4072. doi: 10.1021/bi00772a008. [DOI] [PubMed] [Google Scholar]
  2. Behnke W. D., Teller D. C., Wade R. D., Neurath H. Hybrid formation of carboxypeptidase A and fraction II of procarboxypeptidase A. Biochemistry. 1970 Oct 13;9(21):4189–4200. doi: 10.1021/bi00823a022. [DOI] [PubMed] [Google Scholar]
  3. CHRISTIAN C. L. Characterization of the reactant (gamma globulin factor) in the F II precipitin reaction and the F II tanned sheep cell agglutination test. J Exp Med. 1958 Jul 1;108(1):139–157. doi: 10.1084/jem.108.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crothers D. M., Metzger H. The influence of polyvalency on the binding properties of antibodies. Immunochemistry. 1972 Mar;9(3):341–357. doi: 10.1016/0019-2791(72)90097-3. [DOI] [PubMed] [Google Scholar]
  5. DeRosier D. J., Munk P., Cox D. J. Automatic measurement of interference photographs from the ultracentrifuge. Anal Biochem. 1972 Nov;50(1):139–153. doi: 10.1016/0003-2697(72)90493-9. [DOI] [PubMed] [Google Scholar]
  6. Grey H. M., Kohler P. F., Terry W. D., Franklin E. C. Human monoclonal gamma G-cryoglobulins with anti-gamma-globulin activity. J Clin Invest. 1968 Aug;47(8):1875–1884. doi: 10.1172/JCI105878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. HELMKAMP R. W., GOODLAND R. L., BALE W. F., SPAR I. L., MUTSCHLER L. E. High specific activity iodination of gamma-globulin with iodine-131 monochloride. Cancer Res. 1960 Nov;20:1495–1500. [PubMed] [Google Scholar]
  8. Hannestad K. Presence of aggregated gamma-G-globulin in certain rheumatoid synovial effusions. Clin Exp Immunol. 1967 Jul;2(4):511–529. [PMC free article] [PubMed] [Google Scholar]
  9. KUNKEL H. G., MULLER-EBERHARD H. J., FUDENBERG H. H., TOMASI T. B. Gamma globulin complexes in rheumatoid arthritis and certain other conditions. J Clin Invest. 1961 Jan;40:117–129. doi: 10.1172/JCI104224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kunkel H. G. Experimental approaches tohomogenous antibody populations. iIndividual antigenic specificity, cross specificity and diversity of human antibodies. Fed Proc. 1970 Jan-Feb;29(1):55–58. [PubMed] [Google Scholar]
  11. Mannik M., Stage D. E. Antibody-agarose immunoadsorbents: complete removal of classes of immunoglobulins from serum. J Immunol. 1971 Jun;106(6):1670–1672. [PubMed] [Google Scholar]
  12. Munthe E., Natvig J. B. Characterization of IgG complexes in eluates from rheumatoid tissue. Clin Exp Immunol. 1971 Feb;8(2):249–262. [PMC free article] [PubMed] [Google Scholar]
  13. Munthe E., Natvig J. B. Complement-fixing intracellular complexes of IgG rheumatoid factor in rheumatoid plasma cells. Scand J Immunol. 1972;1(3):217–229. doi: 10.1111/j.1365-3083.1972.tb01813.x. [DOI] [PubMed] [Google Scholar]
  14. NISONOFF A., WISSLER F. C., LIPMAN L. N., WOERNLEY D. L. Separation of univalent fragments from the bivalent rabbit antibody molecule by reduction of disulfide bonds. Arch Biochem Biophys. 1960 Aug;89:230–244. doi: 10.1016/0003-9861(60)90049-7. [DOI] [PubMed] [Google Scholar]
  15. NOELKEN M. E., NELSON C. A., BUCKLEY C. E., 3rd, TANFORD C. GROSS CONFORMATION OF RABBIT 7 S GAMMA-IMMUNOGLOBULIN AND ITS PAPAIN-CLEAVED FRAGMENTS. J Biol Chem. 1965 Jan;240:218–224. [PubMed] [Google Scholar]
  16. Roark D. E., Yphantis D. A. Studies of self-associating systems by equilibrium ultracentrifugation. Ann N Y Acad Sci. 1969 Nov 7;164(1):245–278. doi: 10.1111/j.1749-6632.1969.tb14043.x. [DOI] [PubMed] [Google Scholar]
  17. Schrohenloher R. E. Characterization of the gamma-globulin complexes present in certain sera having high titers of anti-gamma-globulin activity. J Clin Invest. 1966 Apr;45(4):501–512. doi: 10.1172/JCI105364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Teller D. C. Ultracentrifuge study of the self-association of fraction II of procarboxypeptidase A. Biochemistry. 1970 Oct 13;9(21):4201–4209. doi: 10.1021/bi00823a023. [DOI] [PubMed] [Google Scholar]
  19. Van Holde K. E., Rossetti G. P. A sedimentation equilibrium study of the association of purine in aqueous solutions. Biochemistry. 1967 Jul;6(7):2189–2194. doi: 10.1021/bi00859a041. [DOI] [PubMed] [Google Scholar]
  20. Van Holde K. E., Rossetti G. P., Dyson R. D. Sedimentation equilibrium of low-molecular-weight associating solutes. Ann N Y Acad Sci. 1969 Nov 7;164(1):279–293. doi: 10.1111/j.1749-6632.1969.tb14044.x. [DOI] [PubMed] [Google Scholar]
  21. Winchester R. J., Agnello V., Kunkel H. G. Gamma globulin complexes in synovial fluids of patients with rheumatoid arthritis. Partial characterization and relationship to lowered complement levels. Clin Exp Immunol. 1970 May;6(5):689–706. [PMC free article] [PubMed] [Google Scholar]
  22. Winchester R. J., Kunkel H. G., Agnello V. Occurrence of -globulin complexes in serum and joint fluid of rheumatoid arthritis patients: use of monoclonal rheumatoid factors as reagents for their demonstration. J Exp Med. 1971 Sep 1;134(3 Pt 2):286s–295s. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES