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. 1976 Oct;58(4):933–941. doi: 10.1172/JCI108546

Rheumatoid factor-producing cells detected by direct hemolytic plaque assay.

J H Vaughan, T Chihara, T L Moore, D L Robbins, K Tanimoto, J S Johnson, R McMillan
PMCID: PMC333256  PMID: 787010

Abstract

Lymphocytes secreting anti-IgC antibodies, rheumatoid factors (RF), can be detected in the peripheral bloods, synovial fluids, and bone marrows of patients with seropositive rheumatoid arthritis by using a direct plaque-forming cell (PFC) assay with sheep erythrocytes sensitized with reduced and alkylated rabbit IgG hemolysin. The autospecific nature of the RF produced by RF-PFC was indicated by inhibition studies in which the order of patency was human IgG greater than rabbit IgG greater than bovine IgG. In metabolic studies puromycin, cycloheximide, and venblastine suppressed RF-PFC. Cyclic AMP and cyclic GMP were without effect. A need was recognized for using full tissue culture media during the cell separation and plaquing procedures to optimize detection of the RF-PFC. RF-PFC may appear in the blood of patients intermittently despite their continuing presence in the bone marrow. They have been found in the peripheral blood, especially during acutely exacerbating polyarticular synovitis, generalized vasculities, or generally active, aggressive disease. RF-PFC were found in synovial effusions of new or recrduescent acute synovitis. RF-PFC were observed to disappear from the peripheral circulation and the bone marrow during therapy with cytotoxic drugs. The data are consistent with the hypothesis that the appearance of RF-PFC in the peripheral blood represents an anamnestic response to transiently appearing antigen. The nature of the antigen is not specified. The bone marrow may be a site of origin of RF-PFC.

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Selected References

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

  1. BUTLER V. P., Jr, VAUGHAN J. H. HEMAGGLUTINATION BY RHEUMATOID FACTOR OF CELLS COATED WITH ANIMAL GAMMA GLOBULINS. Proc Soc Exp Biol Med. 1964 Jul;116:585–593. doi: 10.3181/00379727-116-29313. [DOI] [PubMed] [Google Scholar]
  2. BUTLER V. P., Jr, VAUGHAN J. H. THE REACTION OF RHEUMATOID FACTOR WITH ANIMAL GAMMA-GLOBULINS: QUANTITATIVE CONSIDERATIONS. Immunology. 1965 Feb;8:144–159. [PMC free article] [PubMed] [Google Scholar]
  3. Bach J. F., Delrieu F., Delbarre F. The rheumatoid rosette. A diagnostic test unifying seropositive and seronegative rheumatoid arthritis. Am J Med. 1970 Aug;49(2):213–222. doi: 10.1016/s0002-9343(70)80077-8. [DOI] [PubMed] [Google Scholar]
  4. Bell D. A., Clark C., Blomgren S. E., Vaughan J. H. Anti DNA antibody production by lymphoid cells of NZB-W mice and human systemic lupus erythematosus (SLE). Clin Immunol Immunopathol. 1973 Apr;1(3):293–303. doi: 10.1016/0090-1229(73)90046-9. [DOI] [PubMed] [Google Scholar]
  5. Benner R., Meima F., van der Meulen G. M., van Muiswinkel W. B. Antibody formation in mouse bone marrow. I. Evidence for the development of plaque-forming cells in situ. Immunology. 1974 Feb;26(2):247–255. [PMC free article] [PubMed] [Google Scholar]
  6. Bensch K. G., Malawista S. E. Microtubular crystals in mammalian cells. J Cell Biol. 1969 Jan;40(1):95–107. doi: 10.1083/jcb.40.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bonomo L., Tursi A., Gillardi U. Distribution of the anti-gamma globulin factors in the synovial membrane and other tissues in various diseases. Ann Rheum Dis. 1968 Mar;27(2):122–129. doi: 10.1136/ard.27.2.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CASSEN B., HITT J., HAYS E. F. The efficient separation of lymphocytes from normal human blood. J Lab Clin Med. 1958 Nov;52(5):778–783. [PubMed] [Google Scholar]
  9. Clagett J. A., Wilson C. B., Weigle W. O. Interstitial immune complex thyroiditis in mice: the role of autoantibody to thyroglobulin. J Exp Med. 1974 Dec 1;140(6):1439–1456. doi: 10.1084/jem.140.6.1439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clinton B. A., Weigle W. E. Cellular events during the induction of experimental thyroiditis in the rabbit. J Exp Med. 1972 Dec 1;136(6):1605–1615. doi: 10.1084/jem.136.6.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Durance R. A., Micheli A., Fallet G. H. Rosette formation in rheumatiod and non-rheumatiod states. Ann Rheum Dis. 1974 May;33(3):216–220. doi: 10.1136/ard.33.3.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. FRIEDMAN H. DISTRIBUTION OF ANTIBODY PLAQUE FORMING CELLS IN VARIOUS TISSUES OF SEVERAL STRAINS OF MICE INJECTED WITH SHEEP ERYTHROCYTES. Proc Soc Exp Biol Med. 1964 Nov;117:526–530. doi: 10.3181/00379727-117-29628. [DOI] [PubMed] [Google Scholar]
  13. Fries J. F., Hess E. V., Klinenberg J. A standard database for rheumatic diseases. Arthritis Rheum. 1974 May-Jun;17(3):327–336. doi: 10.1002/art.1780170319. [DOI] [PubMed] [Google Scholar]
  14. HELLER G., JACOBSON A. S., KOLODNY M. H. A modification of the hemagglutination test for rheumatoid arthritis. Proc Soc Exp Biol Med. 1949 Nov;72(2):316–323. doi: 10.3181/00379727-72-17420. [DOI] [PubMed] [Google Scholar]
  15. Hiramoto R. N., Hamin N. M., Harris H. L. The detection of antibody-containing cells in the blood stream during the IgM cellular antibody response. J Immunol. 1968 Mar;100(3):637–640. [PubMed] [Google Scholar]
  16. LEVINE S. Magnetic techniques for in vitro isolation of leucocytes. Science. 1956 Feb 3;123(3188):185–186. doi: 10.1126/science.123.3188.185-a. [DOI] [PubMed] [Google Scholar]
  17. Luzzati A. L., Lefkovits I., Pernis B. Antibody response by rabbit peripheral blood lymphocytes in microcultures. Eur J Immunol. 1973 Oct;3(10):632–635. doi: 10.1002/eji.1830031008. [DOI] [PubMed] [Google Scholar]
  18. MELLORS R. C., NOWOSLAWSKI A., KORNGOLD L., SENGSON B. L. Rheumatoid factor and the pathogenesis of rheumatoid arthritis. J Exp Med. 1961 Feb 1;113:475–484. doi: 10.1084/jem.113.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McCormick J. N. An Immunofluorescence Study of Rheumatoid Factor. Ann Rheum Dis. 1963 Jan;22(1):1–10. doi: 10.1136/ard.22.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McMillan R., Longmire R. L., Yelenosky R., Lang J. E., Heath V., Craddock C. G. Immunoglobulin synthesis by human lymphoid tissues: normal bone marrow as a major site of IgG production. J Immunol. 1972 Dec;109(6):1386–1394. [PubMed] [Google Scholar]
  21. Micklem H. S., Ford C. E., Evans E. P., Gray J. Interrelationships of myeloid and lymphoid cells: studies with chromosome-marked cells transfused into lethally irradiated mice. Proc R Soc Lond B Biol Sci. 1966 Jul 19;165(998):78–102. doi: 10.1098/rspb.1966.0059. [DOI] [PubMed] [Google Scholar]
  22. Milde E. J., Tönder O. Demonstration of rheumatoid factor in tissue by mixed agglutination with tissue sections. Arthritis Rheum. 1968 Aug;11(4):537–545. doi: 10.1002/art.1780110403. [DOI] [PubMed] [Google Scholar]
  23. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Romball C. G., Weigle W. O. A cyclical appearance of antibody-producing cells after a single injection of serum protein antigen. J Exp Med. 1973 Dec 1;138(6):1426–1442. doi: 10.1084/jem.138.6.1426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Roseman J. M., Leserman L. D., Fitch F. W., Rowley D. A. Do antibody-forming cells circulate in the blood? J Immunol. 1969 Apr;102(4):1002–1007. [PubMed] [Google Scholar]
  26. Smiley J. D., Sachs C., Ziff M. In vitro synthesis of immunoglobulin by rheumatoid synovial membrane. J Clin Invest. 1968 Mar;47(3):624–632. doi: 10.1172/JCI105758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tanimoto K., Cooper N. R., Johnson J. S., Vaughan J. H. Complement fixation by rheumatoid factor. J Clin Invest. 1975 Mar;55(3):437–445. doi: 10.1172/JCI107949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. WALLER M. V., VAUGHAN J. H. Use of anti-Rh sera for demonstrating agglutination activating factor in rheumatoid arthritis. Proc Soc Exp Biol Med. 1956 May;92(1):198–200. doi: 10.3181/00379727-92-22426. [DOI] [PubMed] [Google Scholar]
  29. Zvaifler N. J., Schur P. Reactions of aggregated mercaptoethanol treated gamma globulin with rheumatoid factor--precipitin and complement fixation studies. Arthritis Rheum. 1968 Aug;11(4):523–536. doi: 10.1002/art.1780110402. [DOI] [PubMed] [Google Scholar]

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