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. 1965 Mar 31;121(4):503–519. doi: 10.1084/jem.121.4.503

PROPERTIES OF VARIOUS ANTI-γ-GLOBULIN FACTORS IN HUMAN SERA

Morten Harboe 1, Barbara Rau 1, Kimmo Aho 1
PMCID: PMC2137992  PMID: 14276773

Abstract

The serological and physicochemical properties of the following three forms of human anti-γ-globulin factors were compared: (a) rheumatoid factors; (b) Milgrom type anti-γ-globulin factors; and (c) factors directed against an antigen in human γG-globulin that is hidden in the intact molecule and revealed by enzymatic digestion at low pH. The property common to these factors is ability to interact with human γG-globulin; they are distinguishable because they react with different antigenic groups on this molecule. In all of five sera, the Milgrom type anti-γ-globulin factors were γM-globulins. They reacted with various human γG-globulin antibodies but failed to interact with γM-globulin type antibodies in agglutination and absorption experiments. When isolated from other anti-γ-globulin factors, they agglutinated red cells coated with intact anti-Rh antibodies, but failed to react with cells cells coated with pepsin-digested anti-Rh antibody. These observations indicate that the agglutinator reacts with the crystallizable, inert fragment of γG-globulin. Anti-γ-globulin activity directed against an antigen in human γG-globulin revealed by pepsin digestion was demonstrated in γG-, γA-, and γM-globulins. This anti-γ-globulin factor could be absorbed by antigen-antibody precipitates containing human antibody, which shows that the hidden antigen in human γG-globulin is revealed not only by enzymatic digestion at low pH, but also when γG-globulin is present as antibody in an antigen-antibody precipitate. Rheumatoid factors and Milgrom type anti-γ-globulin factors were also absorbed by antigen-antibody precipitates containing human antibody. The results indicate that the three distinct forms of antiγ-globulin factors may all be produced as a result of antigenic stimulation by autologous antigen-antibody complexes.

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Selected References

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  1. ABRUZZO J. L., CHRISTIAN C. L. The induction of a rheumatoid factor-like substance in rabbits. J Exp Med. 1961 Nov 1;114:791–806. doi: 10.1084/jem.114.5.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. AHO K., HARBOE M., LEIKOLA J. STUDIES OF THE ANTIBODY NATURE OF THE RHEUMATOID FACTOR. REACTION OF THE RHEUMATOID FACTOR WITH SHEEP ERYTHROCYTES SENSITIZED WITH HUMAN ANTI-SHEEP CELL ANTIBODIES AND WITH O RH POSITIVE CELLS SENSITIZED WITH INCOMPLETE ANTI-RH ANTIBODIES. Immunology. 1964 Jul;7:403–418. [PMC free article] [PubMed] [Google Scholar]
  3. AHO K., KONTTINEN A., RAJASALMI M., WAGER O. Transient appearance of the rheumatoid factor in connection with prophylactic vaccinations. Acta Pathol Microbiol Scand. 1962;56:478–479. doi: 10.1111/j.1699-0463.1962.tb04201.x. [DOI] [PubMed] [Google Scholar]
  4. AHO K., LEIKOLA J., SIMONS K. OBSERVATIONS ON HUMAN COMPLETE AND INCOMPLETE 7S GAMMA-GLOBULIN ANTIBODIES AGAINST RED CELLS AND THEIR INTERACTIONS WITH THE RHEUMATOID FACTOR. Acta Pathol Microbiol Scand. 1964;62:589–594. doi: 10.1111/apm.1964.62.4.589. [DOI] [PubMed] [Google Scholar]
  5. AHO K., SIMONS K. STUDIES OF THE ANTIBODY NATURE OF THE RHEUMATOID FACTOR. REACTION OF THE RHEUMATOID FACTOR WITH HUMAN SPECIFIC PRECIPITATES AND WITH NATIVE HUMAN GAMMA GLOBULIN. Arthritis Rheum. 1963 Dec;6:676–688. doi: 10.1002/art.1780060603. [DOI] [PubMed] [Google Scholar]
  6. AHO K., WAGER O. Production of anti-antibodies in rabbits. Ann Med Exp Biol Fenn. 1961;39:79–87. [PubMed] [Google Scholar]
  7. ALLEN J. C., KUNKEL H. G. Antibodies to genetic types of gamma globulin after multiple transfusions. Science. 1963 Feb 1;139(3553):418–419. doi: 10.1126/science.139.3553.418. [DOI] [PubMed] [Google Scholar]
  8. CHRISTIAN C. L. RHEUMATOID FACTOR PROPERTIES OF HYPERIMMUNE RABBIT SERA. J Exp Med. 1963 Nov 1;118:827–844. doi: 10.1084/jem.118.5.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DIXON A. S. "Rheumatoid arthritis" with negative serological reaction. Ann Rheum Dis. 1960 Sep;19:209–228. doi: 10.1136/ard.19.3.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. EDELMAN G. M., KUNKEL H. G., FRANKLIN E. C. Interaction of the rheumatoid factor with antigen-antibody complexes and aggregated gamma globulin. J Exp Med. 1958 Jul 1;108(1):105–120. doi: 10.1084/jem.108.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FRANKLIN E. C., FUDENBERG H., MELTZER M., STANWORTH D. R. The structural basis for genetic variations of normal human gamma-globulins. Proc Natl Acad Sci U S A. 1962 Jun 15;48:914–922. doi: 10.1073/pnas.48.6.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. FUDENBERG H. H., FUDENBERG B. R. ANTIBODY TO HEREDITARY HUMAN GAMMA-GLOBULIN (GM) FACTOR RESULTING FROM MATERNAL-FETAL INCOMPATIBILITY. Science. 1964 Jul 10;145(3628):170–171. doi: 10.1126/science.145.3628.170. [DOI] [PubMed] [Google Scholar]
  13. FUDENBERG H. H., GOODMAN J. W., MILGROM F. IMMUNOCHEMICAL STUDIES ON RABBIT ANTI-ANTIBODY. J Immunol. 1964 Feb;92:227–233. [PubMed] [Google Scholar]
  14. Franklin E. C., Stanworth D. R. ANTIGENIC RELATIONSHIPS BETWEEN IMMUNE GLOBULINS AND CERTAIN RELATED PARAPROTEINS IN MAN. J Exp Med. 1961 Sep 30;114(4):521–533. doi: 10.1084/jem.114.4.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. GOODMAN J. W. Reaction of rheumatoid sera with fragments of papain-digested rabbit gamma globulin. Proc Soc Exp Biol Med. 1961 Apr;106:822–825. doi: 10.3181/00379727-106-26488. [DOI] [PubMed] [Google Scholar]
  16. GROSS D., TERRY W., EPSTEIN W. V. The association of hereditary gamma globulin (a) activity with a fragment of human gamma globulin produced by papain digestion. Biochem Biophys Res Commun. 1962 May 4;7:259–263. doi: 10.1016/0006-291x(62)90186-9. [DOI] [PubMed] [Google Scholar]
  17. GRUBB R. Agglutination of erythrocytes coated with incomplete anti-Rh by certain rheumatoid arthritic sera and some other sera; the existence of human serum groups. Acta Pathol Microbiol Scand. 1956;39(3):195–197. [PubMed] [Google Scholar]
  18. GRUBB R. The Gm groups and their relation to rheumatoid arthritis serology. Arthritis Rheum. 1961 Apr;4:195–202. doi: 10.1002/art.1780040209. [DOI] [PubMed] [Google Scholar]
  19. HARBOE M., LUNDEVALL J. A new type in the Gm system. Acta Pathol Microbiol Scand. 1959;45(4):357–370. doi: 10.1111/j.1699-0463.1959.tb04721.x. [DOI] [PubMed] [Google Scholar]
  20. HARBOE M., OSTERLAND C. K., KUNKEL H. G. Localization of two genetic factors to different areas of gamma-globulin molecules. Science. 1962 Jun 15;136(3520):979–980. doi: 10.1126/science.136.3520.979. [DOI] [PubMed] [Google Scholar]
  21. HELLER G., KOLODNY M. H., LEPOW I. H., JACOBSON A. S., RIVERA M. E., MARKS G. H. The hemagglutination test for rheumatoid arthritis. IV. Characterization of the rheumatoid agglutinating factors by analysis of serum fractions prepared by ethanol fractionation. J Immunol. 1955 May;74(5):340–350. [PubMed] [Google Scholar]
  22. ISHIZAKA K., CAMPBELL D. H. Biologic activity of soluble antigen-antibody complexes. V. Change of optical rotation by the formation of skin reactive complexes. J Immunol. 1959 Sep;83:318–326. [PubMed] [Google Scholar]
  23. Johnson F. H., Wright G. G. Influence of Hydrostatic Pressure on the Denaturation of Staphylococcus Antitoxin at 65 degrees C. Proc Natl Acad Sci U S A. 1946 Feb;32(2):21–25. doi: 10.1073/pnas.32.2.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. KUNKEL H. G., FRANKLIN E. C., MULLER-EBERHARD H. J. Studies on the isolation and characterization of the "rheumatoid factor". J Clin Invest. 1959 Feb;38(2):424–434. doi: 10.1172/JCI103817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. LOSPALLUTO J., MILLER W., Jr, DORWARD B., FINK C. W. The formation of macroglobulin antibodies. I. Studies on adult humans. J Clin Invest. 1962 Jul;41:1415–1421. doi: 10.1172/JCI104596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McCluskey R. T., Miller F., Benacerraf B. SENSITIZATION TO DENATURED AUTOLOGOUS GAMMA GLOBULIN. J Exp Med. 1962 Jan 1;115(1):253–273. doi: 10.1084/jem.115.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. OSTERLAND C. K., HARBOE M., KUNKEL H. G. Anti-gamma-globulin factors in human sera revealed by enzymatic splitting of anti-Rh antibodies. Vox Sang. 1963 Mar-Apr;8:133–152. doi: 10.1111/j.1423-0410.1963.tb03290.x. [DOI] [PubMed] [Google Scholar]
  28. Rous P. THE RELATIVE REACTION WITHIN LIVING MAMMALIAN-TISSUES : II. ON THE MOBILIZATION OF ACID MATERIAL WITHIN CELLS, AND THE REACTION AS INFLUENCED BY THE CELL STATE. J Exp Med. 1925 Feb 28;41(3):399–411. doi: 10.1084/jem.41.3.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. SIMONS K., AHO K., SEPPAELAE P., WAGER O. PURIFICATION OF THE RHEUMATOID FACTOR. Clin Chim Acta. 1964 Jun;9:519–525. doi: 10.1016/0009-8981(64)90116-0. [DOI] [PubMed] [Google Scholar]
  30. STEINBERG A. G., WILSON J. A. Hereditary globulin factors and immune tolerance in man. Science. 1963 Apr 19;140(3564):303–304. doi: 10.1126/science.140.3564.303. [DOI] [PubMed] [Google Scholar]
  31. VAUGHAN J. H., ELLIS P. J., MARSHALL H. Quantitative considerations of the rheumatoid factor. J Immunol. 1958 Sep;81(3):261–269. [PubMed] [Google Scholar]
  32. WILLIAMS R. C., Jr, KUNKEL H. G. Antibodies to rabbit gamma-globulin after immunizing with various preparations of autologous gamma-globulin. Proc Soc Exp Biol Med. 1963 Mar;112:554–561. doi: 10.3181/00379727-112-28104. [DOI] [PubMed] [Google Scholar]
  33. WILLIAMS R. C., Jr, KUNKEL H. G. Rheumatoid factor, complement, and conglutinin aberrations in patients with subacute bacterial endocarditis. J Clin Invest. 1962 Mar;41:666–675. doi: 10.1172/JCI104523. [DOI] [PMC free article] [PubMed] [Google Scholar]

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