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Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;7(1):79–88. doi: 10.1111/j.1582-4934.2003.tb00206.x

Imbalance of peripheral B lymphocytes and NK cells in rheumatoid arthritis

Gina Manda 1,, Monica Neagu 1, Alexandra Livescu 1, Carolina Constantin 1, C Codreanu 2, Alina Radulescu 2
PMCID: PMC6740090  PMID: 12767265

Abstract

The study was focused on several cellular immune disorders correlated with the imbalance between peripheral blood B lymphocytes and NK cells in severe rheumatoid arthritis. By flow cytometry we calculated the proportions of T, T helper, T cytotoxic/suppressor, B lymphocytes and natural killer cells in peripheral blood. The mitogen‐induced proliferation of peripheral lymphocytes was measured by tritium‐labeld uridine incorporation. Experimental data highlight a connection between annomal values of the B to natural killer cells ratio and disorders of the peripheral mononuclear cells concentration. We also showed that the polyclonal proliferation capacity of peripheral lymphocytes in rheumatoid arthritis is solely related to the B to natural killer cells ratio or to the natural killer cells proportion. The study reveals a potential role of the imbalance between proportions of peripheral B lymphocytes and natural killer cells in the immune pathogenesis of rheumatoid arthritis, thus pointing out an interrelation between the adaptive and innate immune systems.

Keywords: rheumatoid arthritis, B lymphocytes, NK cells, lymphocyte proliferation

References

  • 1. Feldmann M., Brennan F.M., Maini R.N., Rheumatoid arthritis, Cell, 83: 307–310, 1996. [DOI] [PubMed] [Google Scholar]
  • 2. Turesson C., Jacobsson L., Bergstrom U., Extra‐articular rheumatoid arthritis prevalence and mortality, Rheumathol., 38: 668–674, 1999. [DOI] [PubMed] [Google Scholar]
  • 3. Firestein G.S., Etiology and pathogenesis of rheumatoid arthritis In: Kelley W.N., Harris E.D., Jr, Rudy S., Sledge C.B., eds., Textbook of Rheumatology, Philadelphia : WB Saunders, 1997. pp. 851–897. [Google Scholar]
  • 4. Schroeder A.E., Greiner A., Seyfert C., Berek C., Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis, Proc. Natl. Acad. Sci. USA, 93: 221–225, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Weyand C.M., New insights into the pathogenesis of rheumatoid arthritis, Rheumatol., 39: 3–8, 2000. [DOI] [PubMed] [Google Scholar]
  • 6. Leandro M.J., Edwards J.C.W., Cambridge G., Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion, Ann. Rheum. Dis., 61: 883–888, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. van Boekel M.A.M., Vossenar E.R., van den Hoogen F.H.J., van Venrooij W.J, Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value, Arthritis Res., 4: 87–93, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Takemura S., Klimiuk P.A., Braun A., Goronzy J.J., Weyand C.M., T cell activation in rheumatoid synovium is B cell dependent, J. Immunol., 167: 4710–4718, 2001. [DOI] [PubMed] [Google Scholar]
  • 9. Abrahams V.M., Cambridge G., Edwards J.C.W., Induction of tumor necrosis factor alpha production by human monocytes: a key role for FcγRIIIa in rheumatoid arthritis, Arthritis Rheum., 43: 608–616, 2000. [DOI] [PubMed] [Google Scholar]
  • 10. Tak P.P., Kummer J.A.M., Hack C.E., Daha M.R., Erkelens G.W., Meinders A.E., Kluin P.M., Breedveld F.C., Granzyme‐positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue, Arthritis Rheum., 37: 1735–1743, 1994. [DOI] [PubMed] [Google Scholar]
  • 11. Musatov M.I., Petrova E.D., Konenkov V.I., The interrelation of expression of HLA class 1 and II proteins and of the cosimulatory proteins CD11a/CD18 and CD16 with the lytic activity of resting and activated natural killer lymphocytes, Tsitologiia, 39: 617–628, 1996. [PubMed] [Google Scholar]
  • 12. Mukai E., Nagashima M., Hirano D., Yoshino S., Comparative study of symptoms and neuroendocrineimmune network mediator levels between rheumatoid arthritis patients and healthy subjects, Clin. Exp. Rheumatol., 18: 585–590, 2000. [PubMed] [Google Scholar]
  • 13. Mendes R., Bromelow K.W., Westby M., Galea‐Lauri J., Smith I.E., O'Brien M.E., Souberbielle B.E., Flow‐cytometric visualisation of cytokine production by CD3‐CD56+ NK cells and CD3+CD56+ NK‐T cells in whole blood, Cytometry, 39: 72–78, 2000. [DOI] [PubMed] [Google Scholar]
  • 14. Warrington K.J., Takemura S., Goronzy J.J., Weyand C.M., CD4+, CD28‐ T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems, Arthritis Rheum, 44: 13–20, 2001. [DOI] [PubMed] [Google Scholar]
  • 15. Nanki T., Lipsky P.E., Cytokine, activation marker and chemokine receptor expression by individual CD4+ memory T cells in rheumatoid arthritis synovium, Arthritis Res., 2: 415–429, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Voswinkel J., Weisgerber K., Pfreunschuh M., Gause A., The B lymphocyte in rheumatoid arthritis: recirculation of B lymphocytes between different joints and blood, Autoimmunity, 31: 25–34, 1999. [DOI] [PubMed] [Google Scholar]
  • 17. Medzhitov R., Janeway C.A. Jr, Innate immunity: impact on the adaptative immune response, Curr. Op. Immunol., 9: 4–9, 1997. [DOI] [PubMed] [Google Scholar]
  • 18. Arnett F.C., Edworthy S.M., Bloch D.A., McShane D.J., Fries J.F., Cooper N.S., Healey L.A., Kaplan S.R. et al., The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum., 31: 315–324, 1988. [DOI] [PubMed] [Google Scholar]
  • 19. Boyum A., Isolation of mononuclear cells and granulocytes from human blood, Scand. J. Clin. Lab. Invest., 97: 77–89, 1968. [PubMed] [Google Scholar]
  • 20. Hong R., Assesment of T and B lymphocytes in primary immunodeficiency In: Rose N.R., de Macario E.C., Fahey J.L., Freedman H., Penn G.M., eds., Manual of Clinical Laboratory Immunology (4th edition), American Society for Microbiology, Washington DC , 1992, pp. 387–399. [Google Scholar]
  • 21. Saxon A., Functional B‐cell studies In: Rose N.R., de Macario E.C., Fahey J.L., Freedman H., Penn G.M., eds., Manual of Clinical Laboratory Immunology (4th edition), American Society for Microbiology, Washington DC , 1992, pp. 403–408. [Google Scholar]
  • 22. Neagu M., Manda G., Constantin C., Tanaseanu C., Mikhailidis D.P., The in vitro effect of a low molecular weight heparin, nadroparin (Fraxiparine) on leukocytes obtained from patients with vascular disorders, Int. Angiol., 20: 164–173, 2001. [PubMed] [Google Scholar]
  • 23. Barland P., Lipstein E., Selection and use of laboratory tests in the reumatic diseases, Am. J. Med., 100: 16S–23S, 1996. [DOI] [PubMed] [Google Scholar]
  • 24. Kuryliszyn‐Moskal A., Comparison of blood and synovial fluid lymphocyte subsets in rheumatoid arthritis and osteoarthritis, Clin. Rheumatol., 14: 43–50, 1995. [DOI] [PubMed] [Google Scholar]
  • 25. Wagner U., Kaltenhauser S., Pierer M., Wilke B., Arnold S., B lymphocytopenia in rheumatoid arthritis is associated with DRB1 shared epitope and increased acute phase response, Arthritis Res., 4: R1, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. D'Orazio J.A., Stein‐Streilein J., Human natural killer (NK) cells present staphilococcal enterotoxin B (SEB) to T lymphocytes, Clin. Exp. Immunol., 104: 366–373, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Hendrich C., Kuipers J.G., Kolanus W., Hammer M., Schmidt R.E., Activation of CD16+ effector cells by rheumatoid arthritis factor complex. Role of natural killer cells in rheumatoid arthritis, Arthritis Rheum., 34: 423–431, 1992. [DOI] [PubMed] [Google Scholar]
  • 28. Santiago‐Schwartz F., Kay C., Panagiotopoulos C., Carsons S.E., Rheumatoid arthritis serum or synovial fluid and interleukin 2 abnormally expand natural killer‐like cells that are potent stimulators of IgM rheumatoid factor, J. Rheumatol., 19: 223–228, 1992. [PubMed] [Google Scholar]

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