Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Apr;53(4):1108–1114. doi: 10.1172/JCI107648

Enhancement of Human Lymphocyte Transformation by Aggregated Human Gamma Globulin

T Douglas Kinsella 1
PMCID: PMC333096  PMID: 4131162

Abstract

The effect of heat-aggregated human gamma globulin (aggFII) on the induction of in vitro lymphocyte transformation, measured by the uptake of tritiated thymidine into newly synthesized DNA, was studied with peripheral blood lymphocytes derived from 12 patients with rheumatoid arthritis (RA), six with ankylosing spondylitis (AS), two with systemic lupus erythematosus (SLE), and seven normal subjects. It was found that 200 μg aggFII induced significant transformation of the lymphocytes of eight patients with RA, five with AS, one with SLE, and one normal subject. Neither deaggregated FII nor heat-aggregated human serum albumin induced significant transformation of the lymphocytes of any subject tested. A source of complement appeared necessary to support aggFII-induced blastogenesis, since enhanced transformation occurred only in the presence of fresh plasma. Heat-inactivated plasma and fetal calf serum (FCS), and FCS devoid of hemolytic complement, failed to support enhanced blastogenesis in the presence of aggFII. Since substrates similar to those employed in these studies are present in vivo in the rheumatoid joint, it is suggested that aggFII may enhance intra-articular lymphocyte transformation in subjects with RA.

Full text

PDF
1108

Selected References

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

  1. Anderson S. G., Bentzon M. W., Houba V., Krag P. International reference preparation of rheumatoid arthritis serum. Bull World Health Organ. 1970;42(2):311–318. [PMC free article] [PubMed] [Google Scholar]
  2. Bianco C., Patrick R., Nussenzweig V. A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J Exp Med. 1970 Oct 1;132(4):702–720. doi: 10.1084/jem.132.4.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bozsoky S., Franklin E. C. The effects of chemical modifications of human gamma-globulins on their interaction with rheumatoid factors and antibodies. Arthritis Rheum. 1966 Jun;9(3):405–413. doi: 10.1002/art.1780090305. [DOI] [PubMed] [Google Scholar]
  4. CHRISTIAN C. L. Studies of aggregated gamma-globulin. I. Sedimentation, electrophoretic and anticomplementary properties. J Immunol. 1960 Jan;84:112–116. [PubMed] [Google Scholar]
  5. Chamberlain M. A., Shapland C. G., Roitt I. M. Response to autologous immunoglobulin G in patients with rheumatoid arthritis. Ann Rheum Dis. 1970 Mar;29(2):173–177. doi: 10.1136/ard.29.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Craddock C. G., Longmire R., McMillan R. Lymphocytes and the immune response. I. N Engl J Med. 1971 Aug 5;285(6):324–331. doi: 10.1056/NEJM197108052850606. [DOI] [PubMed] [Google Scholar]
  7. Dickler H. B., Kunkel H. G. Interaction of aggregated -globulin with B lymphocytes. J Exp Med. 1972 Jul 1;136(1):191–196. doi: 10.1084/jem.136.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dukor P., Hartmann K. U. Hypothesis. Bound C3 as the second signal for B-cell activation. Cell Immunol. 1973 Jun;7(3):349–356. doi: 10.1016/0008-8749(73)90199-8. [DOI] [PubMed] [Google Scholar]
  9. HOLLANDER J. L., MCCARTY D. J., Jr, ASTORGA G., CASTRO-MURILLO E. STUDIES ON THE PATHOGENESIS OF RHEUMATOID JOINT INFLAMMATION. I. THE "R.A. CELL" AND A WORKING HYPOTHESIS. Ann Intern Med. 1965 Feb;62:271–280. doi: 10.7326/0003-4819-62-2-271. [DOI] [PubMed] [Google Scholar]
  10. Janossy G., Greaves M. F. Lymphocyte activation. I. Response of T and B lymphocytes to phytomitogens. Clin Exp Immunol. 1971 Oct;9(4):483–498. [PMC free article] [PubMed] [Google Scholar]
  11. KUNKEL H. G., TAN E. M. AUTOANTIBODIES AND DISEASE. Adv Immunol. 1964;27:351–395. doi: 10.1016/s0065-2776(08)60711-7. [DOI] [PubMed] [Google Scholar]
  12. Kacaki J. N., Bullock W. E., Vaughan J. H. Failure of lymphocyte transformation in response to gamma-globulins in rheumatoid arthritis. Lancet. 1969 Jun 28;1(7609):1289–1290. doi: 10.1016/s0140-6736(69)92224-7. [DOI] [PubMed] [Google Scholar]
  13. King R. A., Messner R. P., Williams R. C., Jr Human lymphocyte transformation induced by anti-gamma globulin factors. Arthritis Rheum. 1969 Dec;12(6):597–607. doi: 10.1002/art.1780120607. [DOI] [PubMed] [Google Scholar]
  14. Kinsella T. D., Baum J., Ziff M. Immunofluorescent demonstration of an IgG-B1C complex in synovial lining cells of rheumatoid synovial membrane. Clin Exp Immunol. 1969 Feb;4(2):265–271. [PMC free article] [PubMed] [Google Scholar]
  15. Kinsella T. D. Induction of autologous lymphocyte transformation by synovial fluids from patients with rheumatoid arthritis. Clin Exp Immunol. 1973 Jun;14(2):187–191. [PMC free article] [PubMed] [Google Scholar]
  16. Lang P. G., Ada G. L. The localization of heat denatured serum albumin in rat lymph nodes. Aust J Exp Biol Med Sci. 1967 Aug;45(4):445–448. doi: 10.1038/icb.1967.43. [DOI] [PubMed] [Google Scholar]
  17. Möller G. Induction of DNA synthesis in normal human lymphocyte cultures by antigen-antibody complexes. Clin Exp Immunol. 1969 Jan;4(1):65–82. [PMC free article] [PubMed] [Google Scholar]
  18. OUCHTERLONY O. Diffusion-in-gel methods for immunological analysis. II. Prog Allergy. 1962;6:30–154. doi: 10.1159/000313795. [DOI] [PubMed] [Google Scholar]
  19. RESTIFO R. A., LUSSIER A. J., RAWSON A. J., ROCKEY J. H., HOLLANDER J. L. STUDIES ON THE PATHOGENESIS OF RHEUMATOID JOINT INFLAMMATION. 3. THE EXPERIMENTAL PRODUCTION OF ARTHRITIS BY THE INTRA-ARTICULAR INJECTION OF PURIFIED 7S GAMMA GLOBULIN. Ann Intern Med. 1965 Feb;62:285–291. doi: 10.7326/0003-4819-62-2-285. [DOI] [PubMed] [Google Scholar]
  20. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  21. Reynolds M. D., Abdou N. I. Comparative study of the in vitro proliferative responses of blood and synovial fluid leukocytes of rheumatoid arthritis patients. J Clin Invest. 1973 Jul;52(7):1627–1631. doi: 10.1172/JCI107341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ruddy S., Gigli I., Austen K. F. The complement system of man. I. N Engl J Med. 1972 Sep 7;287(10):489–495. doi: 10.1056/NEJM197209072871005. [DOI] [PubMed] [Google Scholar]
  23. Runge L. A., Mills J. A. In vivo and in vitro responses to autologous IgG in patients with rheumatoid arthritis. Arthritis Rheum. 1971 Sep-Oct;14(5):631–638. doi: 10.1002/art.1780140510. [DOI] [PubMed] [Google Scholar]
  24. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  25. Sliwinski A. J., Zvaifler N. J. The removal of aggregated and nonaggregated autologous gamma globulin from rheumatoid joints. Arthritis Rheum. 1969 Oct;12(5):504–514. doi: 10.1002/art.1780120507. [DOI] [PubMed] [Google Scholar]
  26. Townes A. S., Marcus R. L. Complement-fixing activity of rheumatoid synovial fluid. Ann Rheum Dis. 1972 Sep;31(5):393–401. doi: 10.1136/ard.31.5.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zvaifler N. J. Breakdown products of C 3 in human synovial fluids. J Clin Invest. 1969 Aug;48(8):1532–1542. doi: 10.1172/JCI106119. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES