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Analysis of bcl-2+ lymphocyte subpopulations in inflammatory synovial infiltrates by a double-immunostaining technique

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Abstract

We used a double-immunostaining technique to analyze the distribution of bcl-2+ B and T lymphocytes within the synovial membranes (SM) of 13 patients with rheumatic diseases: 11 with rheumatoid arthritis (RA), 1 with ankylosing spondylitis (AS), and 1 with osteoarthritis (OA). A high proportion (up to 50%) of the lymphocytes belonged to the B cell subset. Most of both T and B lymphocytes were positive for the bcl-2 protein. In germinal centers B lymphocytes were also negative for bcl-2 protein expression, comparable to the situation in germinal centers of secondary lymphatic organs. We conclude that bcl-2+ B lymphocytes are submitted to antigen selection in the inflamed SMs while bcl-2+ protein expression provides survival signals for their persistence in the infiltrates. The expression of bel-2 may be an important factor in protecting lymphocytes in SM from apoptosis by glucocorticoids, cytostatic drugs, and irradiation.

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References

  1. Duke O, Panayi GS, Janossy G, Poulter LW (1982) An immunohistological analysis of lymphocyte subpopulations and their microenvironment in the synovial membranes of patients with rheumatoid arthritis using monoclonal antibodies. Clin Exp Immunol 49:22–30

    PubMed  Google Scholar 

  2. Geiler G (1980) The pathogenesis of rheumatoid arthritis (in German). Z Gesamte Inn Med 35 [Suppl]:152–157

    PubMed  Google Scholar 

  3. Rooney M, Condell D, Quinlan W, Daly L, Whelan A, Feighery C, Bresnihan B (1988) Analysis of the histologic variation of synovitis in rheumatoid arthritis. Arthritis Rheum 31:956–963

    PubMed  Google Scholar 

  4. Goronzy JJ, Weyand CM (1995) T and B cell-dependent pathways in rheumatoid arthritis. Curr Opin Rheumatol 7:214–221

    PubMed  Google Scholar 

  5. Randen I, Mellbye OJ, Forre O, Natvig JB (1995) The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue. Scand J Immunol 41:481–486

    PubMed  Google Scholar 

  6. Cory S (1995) Regulation of lymphocyte survival by the bel-2 gene family. Annu Rev Immunol 13:513–543

    PubMed  Google Scholar 

  7. Oltvai ZN, Korsmeyer SJ (1994) Checkpoints of dueling dimers foil death wishes [comment]. Cell 79:189–192

    PubMed  Google Scholar 

  8. Pfreundschuh M, Mommertz E, Meissner M, Feller AC, Hassa R, Krueger GR, Diehl V (1988) Hodgkin and Reed-Sternberg cell associated monoclonal antibodies HRS-1 and HRS-2 react with activated cells of lymphoid and monocytoid origin. Anticancer Res 8:217–224

    PubMed  Google Scholar 

  9. Mason DY, Abdulaziz Z, Falini B, Stein H (1983) Double immunoenzymatic labelling. In: Polak M, Van Noorden S (eds) Immunocytochemistry. Practical Applications in Pathology and Biology. Wright, Bristol, pp 113–128

    Google Scholar 

  10. Burmester GR, Locher P, Koch B, Winchester RJ, Dimitriu Bona A, Kalden JR, Mohr W (1983) The tissue architecture of synovial membranes in inflammatory and non-inflammatory joint diseases. I. The localization of the major synovial cell populations as detected by monoclonal reagents directed towards la and monocyte-macrophage antigens. Rheumatol Int 3:173–181

    PubMed  Google Scholar 

  11. Janossy G, Panayi G, Duke O, Bofill M, Poulter LW, Goldstein G (1981) Rheumatoid arthritis: a disease of T lymphocyte/macrophage immunoreagulation. Lancet II:839–842

    Google Scholar 

  12. Fassbender HG (1975) Chronische Polyarthritis. In: Fassbender HG (ed) Pathologie rheumatischer Erkrankungen. Springer, Berlin Heidelberg New York, pp 183–224

    Google Scholar 

  13. Fassbender HG (1975) Arthrose. In: Fassbender HG (ed) Pathologie rheumatischer Erkrankungen. Springer, Berlin Heidelberg New York, pp 295–318

    Google Scholar 

  14. Fassbender HG (1975) Spondylitis ankylopoetica. In: Fassbender HG (ed) Pathologie rheumatischer Erkrankungen. Springer, Berlin Heidelberg New York, pp 235–259

    Google Scholar 

  15. Rooney M, Whelan A, Feighery C, Bresnihan B (1989) The immunohistologic features of synovitis, disease activity and in vitro IgM rheumatoid factor synthesis by blood mononuclear cells in rheumatoid arthritis. J Rheumatol 16:459–467

    PubMed  Google Scholar 

  16. Arend WP, Dayer JM (1990) Cytokines and cytokine inhibitors of antagonists in rheumatoid arthritis. Arthritis Rheum 33:305–315

    PubMed  Google Scholar 

  17. Miossec P, Briolay J, Dechanet J, Wijdenes J, Martinez Valdez H, Banchereau J (1992) Inhibition of the product of proinflammatory cytokines and immunoglobulins by interleukin-4 in an ex vivo model of rheumatoid synovitis. Arthritis Rheum 35:874–883

    PubMed  Google Scholar 

  18. Katsikis PD, Chu CQ, Brennan FM, Maim RN, Feldmann M (1994) Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med 179:1517–1527

    PubMed  Google Scholar 

  19. Firestein GS, Yeo M, Zvaifler NJ (1995) Apoptosis in rheumatoid arthritis synovium. J Clin Invest 96:1631–1638

    PubMed  Google Scholar 

  20. Akbar AN, Salmon M, Savill J, Janossy G (1993) A possible role for bel-2 in regulating T-cell memory — a ‘balancing act’ between cell death and survival. Immunol Today 14:526–532

    PubMed  Google Scholar 

  21. Levine B, Huang Q, Isaacs JT, Reed JC, Griffin DE, Hardwick JM (1993) Conversion of lytic to persistent alphavirus infection by the bcl-2+ cellular oncogene. Nature 361:739–742

    PubMed  Google Scholar 

  22. Henderson S, Rowe M, Gregory C, Croom Carter D, Wang F, Longnecker R, Kieff E, Rickinson A (1991) Induction of bel-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115

    PubMed  Google Scholar 

  23. Cush JJ, Lipsky PE (1991) Cellular basis for rheumatoid inflammation. Clin Orthop 9–22

  24. Liu YJ, Mason DY, Johnson GD, Abbot S, Gregory CD, Hardie DL, Gordon J, MacLennan IC (1991) Germinal center cells express bcl-2+ protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol 21:1905–1910

    PubMed  Google Scholar 

  25. Chleq Deschamps CM, LeBrun DP, Huie P, Besnier DP, Warnke RA, Sibley RK, Cleary ML (1993) Topographical dissociation of BCL-2 messenger RNA and protein expression inhuman lymphoid tissues. Blood 81:293–298

    PubMed  Google Scholar 

  26. Berek C (1992) The development of B cells and the B-cell repertoire in the microenvironment of the germinal center. Immunol Rev 126:5–19

    PubMed  Google Scholar 

  27. Leanderson T, Kallberg E, Gray D (1992) Expansion, selection and mutation of antigen-specific B cells in germinal centers. Immunol Rev 126:47–61

    PubMed  Google Scholar 

  28. Korsmeyer SJ (1992) Bcl-2: a repressor of lymphocyte death. Immunol Today 13:285–288

    PubMed  Google Scholar 

  29. Gause A, Gundlach K, Zdichavsky M, Jacobs G, Koch B, Hopf T, Pfreundschuh M (1995) The B lymphocyte in rheumatoid arthritis: analysis of rearranged Vk genes from B cells infiltrating the synovial membrane. Eur J Immunol 25:2775–2782

    PubMed  Google Scholar 

  30. Schröder AE, Greiner A, Seyfert C, Berek C (1996) Differentiation of B cells in the non-lymphoid tissue of the synovial membrane of patients with rheumatoid arthritis. Proc Natl Acad Sci USA 93:221–225

    PubMed  Google Scholar 

  31. MacLennan IC, Liu YJ, Johnson GD (1992) Maturation and dispersal of B-cell clones during T cell-dependent antibody responses. Immunol Rev 126:143–161

    PubMed  Google Scholar 

  32. Lalor PA, Mapp PI, Hall PA, Revell PA (1987) Proliferative activity of cells in the synovium as demonstrated by a monoclonal antibody, Ki67. Rheumatol Int 7:183–186

    PubMed  Google Scholar 

  33. Sack U, Stiehl P, Geiler G (1994) Distribution of macrophages in rheumatoid synovial membrane and its association with basic activity. Rheumatol Int 13:181–186

    PubMed  Google Scholar 

  34. Smith KGC, Weiss U, Rajewsky K, Nossal GJV, Tarlinton DM (1994) Bcl-2 increases memory b cell recruitment but does not perturb selection in germinal centers. Immunity 9:803–813

    Google Scholar 

  35. Merino R, Ding L, Veis DJ, Korsmeyer SJ, Nunez G (1994) Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes. EMBO J 13:683–691

    PubMed  Google Scholar 

  36. Hockenbery DM (1992) The bcl-2+ oncogene and apoptosis. Semin Immunol 4:413–420

    PubMed  Google Scholar 

  37. Maim RN, Plater Zyberk C, Andrew E (1987) Autoimmunity in rheumatoid arthritis. An approach via a study of B lymphocytes. Rheum Dis Clin North Am 13:319–338

    PubMed  Google Scholar 

  38. Young CL, Adamson TC, Vaughan JH, Fox RI (1984) Immunohistologic characterization of synovial membrane lymphocytes in rheumatoid arthritis. Arthritis Rheum 27:32–39

    PubMed  Google Scholar 

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Zdichavsky, M., Schorpp, C., Nickels, A. et al. Analysis of bcl-2+ lymphocyte subpopulations in inflammatory synovial infiltrates by a double-immunostaining technique. Rheumatol Int 16, 151–157 (1996). https://doi.org/10.1007/BF01419728

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  • DOI: https://doi.org/10.1007/BF01419728

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