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J Clin Invest. Jun 1984; 73(6): 1789–1795.
PMCID: PMC437092

Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis.


Patients with rheumatoid arthritis (RA) are known to have in vitro regulatory T cell abnormalities relating to Epstein-Barr virus (EBV). In this report, we asked whether patients with RA have more circulating EBV-infected B cells than normals. To address this question, we determined the frequency of spontaneously transforming B cells in the peripheral blood of 18 normals, 15 patients with RA, and 8 patients with systemic lupus erythematosus (SLE). The mean frequency of spontaneously transforming B cells in RA patients was 10.1/10(6) B cells, which was significantly greater than that of the normal controls, 2.8/10(6) B cells (P less than 0.005). The group of patients with SLE did not differ from the normals (P greater than 0.4). In further studies undertaken to investigate as to whether RA B cells are more easily transformed by EBV than normal B cells, we determined that the frequencies of transforming B cells in the presence of exogenous EBV were similar in RA patients and normals. Lymphocytes obtained from patients with RA demonstrate a profound T cell defect in their EBV-specific suppression, as measured in vitro; there was no direct correlation, however, between this in vitro T cell abnormality and the number of circulating EBV-infected B cells. Thus, patients with RA, as a group, have abnormally elevated numbers of circulating EBV-infected B cells, and this abnormality most likely derives from a complex dysregulation of the defense mechanisms for infection with EBV.

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Selected References

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  • Jondal M, Klein G. Surface markers on human B and T lymphocytes. II. Presence of Epstein-Barr virus receptors on B lymphocytes. J Exp Med. 1973 Dec 1;138(6):1365–1378. [PMC free article] [PubMed]
  • Rosén A, Gergely P, Jondal M, Klein G, Britton S. Polyclonal Ig production after Epstein-Barr virus infection of human lymphocytes in vitro. Nature. 1977 May 5;267(5606):52–54. [PubMed]
  • Henle W, Diehl V, Kohn G, Zur Hausen H, Henle G. Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Science. 1967 Sep 1;157(3792):1064–1065. [PubMed]
  • Diehl V, Henle G, Henle W, Kohn G. Demonstration of a herpes group virus in cultures of peripheral leukocytes from patients with infectious mononucleosis. J Virol. 1968 Jul;2(7):663–669. [PMC free article] [PubMed]
  • Thorley-Lawson DA, Chess L, Strominger JL. Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes. J Exp Med. 1977 Aug 1;146(2):495–508. [PMC free article] [PubMed]
  • Thorley-Lawson DA. The suppression of Epstein-Barr virus infection in vitro occurs after infection but before transformation of the cell. J Immunol. 1980 Feb;124(2):745–751. [PubMed]
  • Rickinson AB, Wallace LE, Epstein MA. HLA-restricted T-cell recognition of Epstein-Barr virus-infected B cells. Nature. 1980 Feb 28;283(5750):865–867. [PubMed]
  • Tosato G, Magrath IT, Blaese RM. T cell-mediated immunoregulation of Epstein Barr virus- (EBV) induced B lymphocyte activation in EBV-seropositive and EBV-seronegative individuals. J Immunol. 1982 Feb;128(2):575–579. [PubMed]
  • Alspaugh MA, Jensen FC, Rabin H, Tan EM. Lymphocytes transformed by Epstein-Barr virus. Induction of nuclear antigen reactive with antibody in rheumatoid arthritis. J Exp Med. 1978 Apr 1;147(4):1018–1027. [PMC free article] [PubMed]
  • Alspaugh MA, Henle G, Lennette ET, Henle W. Elevated levels of antibodies to Epstein-Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis. J Clin Invest. 1981 Apr;67(4):1134–1140. [PMC free article] [PubMed]
  • Slaughter L, Carson DA, Jensen FC, Holbrook TL, Vaughan JH. In vitro effects of Epstein-Barr virus on peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal subjects. J Exp Med. 1978 Nov 1;148(5):1429–1434. [PMC free article] [PubMed]
  • Bardwick PA, Bluestein HG, Zvaifler NJ, Depper JM, Seegmiller JE. Altered regulation of Epstein-Barr virus induced lymphoblast proliferation in rheumatoid arthritis lymphoid cells. Arthritis Rheum. 1980 Jun;23(6):626–632. [PubMed]
  • Depper JM, Bluestein HG, Zvaifler NJ. Impaired regulation of Epstein-Barr virus-induced lymphocyte proliferation in rheumatoid arthritis is due to a T cell defect. J Immunol. 1981 Nov;127(5):1899–1902. [PubMed]
  • Tosato G, Steinberg AD, Blaese RM. Defective EBV-specific suppressor T-cell function in rheumatoid arthritis. N Engl J Med. 1981 Nov 19;305(21):1238–1243. [PubMed]
  • Henle G, Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. [PMC free article] [PubMed]
  • Tosato G, Pike SE, Koski IR, Blaese RM. Selective inhibition of immunoregulatory cell functions by cyclosporin A. J Immunol. 1982 May;128(5):1986–1991. [PubMed]
  • Yarchoan R, Tosato G, Blaese RM, Simon RM, Nelson DL. Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells. J Exp Med. 1983 Jan 1;157(1):1–14. [PMC free article] [PubMed]
  • Bird AG, McLachlan SM, Britton S. Cyclosporin A promotes spontaneous outgrowth in vitro of Epstein-Barr virus-induced B-cell lines. Nature. 1981 Jan 22;289(5795):300–301. [PubMed]
  • Heller M, Henderson A, Kieff E. Repeat array in Epstein-Barr virus DNA is related to cell DNA sequences interspersed on human chromosomes. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5916–5920. [PMC free article] [PubMed]
  • Henderson E, Miller G, Robinson J, Heston L. Efficiency of transformation of lymphocytes by Epstein-Barr virus. Virology. 1977 Jan;76(1):152–163. [PubMed]
  • Robinson JE, Smith D, Niederman J. Plasmacytic differentiation of circulating Epstein-Barr virus-infected B lymphocytes during acute infectious mononucleosis. J Exp Med. 1981 Feb 1;153(2):235–244. [PMC free article] [PubMed]
  • Rocchi G, Felici A, Ragona G, Heinz A. Quantitative evaluation of Epstein-Barr-virus-infected mononuclear peripheral blood leukocytes in infectious mononucleosis. N Engl J Med. 1977 Jan 20;296(3):132–134. [PubMed]
  • Moss DJ, Rickinson AB, Wallace LE, Epstein MA. Sequential appearance of Epstein-Barr virus nuclear and lymphocyte-detected membrane antigens in B cell transformation. Nature. 1981 Jun 25;291(5817):664–666. [PubMed]
  • Gerber P, Lucas S, Nonoyama M, Perlin E, Goldstein LI. Oral excretion of Epstein-Barr virus by healthy subjects and patients with infectious mononucleosis. Lancet. 1972 Nov 11;2(7785):988–989. [PubMed]
  • Depper JM, Zvaifler NJ. Epstein-Barr virus. Its relationship to the pathogenesis of rheumatoid arthritis. Arthritis Rheum. 1981 Jun;24(6):755–761. [PubMed]
  • Masucci MG, Bejarano MT, Masucci G, Klein E. Large granular lymphocytes inhibit the in vitro growth of autologous Epstein-Barr virus-infected B cells. Cell Immunol. 1983 Mar;76(2):311–321. [PubMed]
  • Tsoukas CD, Carson DA, Fong S, Slovin SF, Fox RI, Vaughan JH. Lysis of autologous Epstein-Barr virus-infected B cells by cytotoxic T lymphocytes of rheumatoid arthritis patients. Clin Immunol Immunopathol. 1982 Jul;24(1):8–14. [PubMed]

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