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The role of apoptosis in antibody-dependent cellular cytotoxicity

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Abstract

Apoptosis in three lymphoma cell lines has been studied following cytotoxicity induced in vitro by normal human blood lymphocytes utilizing either natural killer (NK) or antibody-dependent cellular cytotoxic (ADCC) mechanisms. Guinea-pig L2C leukaemic lymphocytes, but not the human cell lines Daudi and Jurkat, revealed a degree of time- and temperature-dependent apoptotic death upon simple culture in vitro. NK cytotoxicity at low effector: target ratios (E: T) induced both release of51Cr and apoptosis. However NK cytotoxicity at higher E : T, and ADCC at all E : T, increased the level of51Cr release while reducing the level of apoptosis. The findings were consistent with the apoptotic process being cut short by intervention of necrotic death. The same characteristics accompanied ADCC whether the effectors were recruited by Fcγ regions of antibody coating the targets, or by bispecific antibodies attaching one arm to the targets and the other to Fcγ receptors type III on effectors. This finding, and the high level of cytotoxicity elicited by the bispecific method, confirm the belief that NK cells, in addition to exerting NK cytotoxicity, represent the principal effectors for ADCC among blood mononuclear cells. Our results suggest that NK cells have both apoptotic and necrotic mechanisms available for killing their targets, but use only the latter for ADCC.

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References

  1. Baxter GD, Collins RJ, Harmon BV, Kumar S, Prentice RL, Smith PJ, Lavin MF (1989) Cell death by apoptosis in acute leukaemia. J Pathol 158: 123–129

    Google Scholar 

  2. Berke G (1991) Lymphocyte-triggered internal target disintegration. Immunol Today 12: 396–399

    Google Scholar 

  3. Collins RJ, Verschuer LA, Harmon BV, Prentice RL, Pope JH, Kerr JF (1989) Spontaneous programmed cell death (apoptosis) of B-chronic lymphocytic leukaemia cells following their culture in vitro. Br J Haematol 71: 343–350

    Google Scholar 

  4. Duke RC, Chervenak R, Cohen JJ (1983) Endogenous endonucleaseinduced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci USA 80: 6361–6365

    Google Scholar 

  5. Duke RC, Cohen JJ, Chervanek R (1986) Differences in target cell DNA fragmentation induced by mouse cytotoxic T lymphocytes and natural killer cells. J Immunol 137: 1442–1447

    Google Scholar 

  6. Duke RC, Persechini PM, Chang S, Liu CC, Cohen JJ, Young JD (1989) Purified perforin induces target cell lysis but not DNA fragmentation. J Exp Med 170: 1451–1456

    Google Scholar 

  7. Duvall E, Wyllie AH, Morris RG (1985) Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunol 56: 351–358

    Google Scholar 

  8. Elliott TJ, Glennie MJ, McBride HM, Stevenson GT (1987) Analysis of the interaction of antibodies with immunoglobulin idiotypes on neoplastic B lymphocytes; implications for immunotherapy. J Immunol 138: 981–988

    Google Scholar 

  9. Fleit HB, Wright SD, Unkeless JC (1982) Human Fc gamma receptor distribution and structure. Proc Natl Acad Sci USA 79: 3275–3280

    Google Scholar 

  10. Glennie MJ, McBride HM, Worth AT, Stevenson GT (1987) Preparation and performance of bispecific F(ab′γ)2 antibody containing thioether-linked Fab′γ fragments. J Immunol 139: 2367–2375

    Google Scholar 

  11. Greenman J, Hogg NM, Nikoletti SM, Slade CJ, Stevenson GT, Glennie MJ (1992) Comparative efficiencies of bispecific F(ab′γ)2 and chimeric mouse/human IgG antibodies in recruiting cellular effectors for cytotoxicity via Fcγ receptors. Cancer Immunol Immunother 34: 361–369

    Google Scholar 

  12. Gromkowski SH, Brown TC, Cerutti PA, Cerottini JC (1986) DNA of human Raji target cells is damaged upon lymphocyte-mediated lysis. J Immunol 136: 752–756

    Google Scholar 

  13. Ishigami T, Kim KM, Horiguchi Y, Higaki Y, Hata D, Heike T, Katamura K, Mayumi M, Mikawa H (1992) Anti-IgM antibody-induced cell death in a human B-lymphoma cell line, B104, represents a novel programmed cell death. J Immunol 148: 360–368

    Google Scholar 

  14. Karpovsky B, Titus JA, Stephany DA, Segal DM (1984) Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fcγ receptor antibodies. J Exp Med 160: 1686–1701

    Google Scholar 

  15. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications for tissue kinetics. Br J Cancer 26: 239–257

    Google Scholar 

  16. Klein E, Klein G, Nadkarni JS, Nadkarni JJ, Wigzell H, Clifford P (1968) Surface IgM-kappa specificity on a Burkitt lymphoma cell line in vivo and in derived culture lines. Cancer Res 28: 1300–1310

    Google Scholar 

  17. Krahenbuhl O, Tschopp J (1991) Perforin-induced pore formation. Immunol Today 12: 399–403

    Google Scholar 

  18. Lamoyi E, Nisonoff A (1983) Preparation of F(ab′)2 fragments from mouse IgG of various subclasses. J Immunol Methods 56: 235–243

    Google Scholar 

  19. Liu Y, Mullbacher A, Waring P (1989) Natural killer cells and cytotoxic T cells induce DNA fragmentation in both human and murine target cells in vitro. Scand J Immunol 30: 31–37

    Google Scholar 

  20. McConkey DJ, Chow SC, Orrenius S, Jondal M (1990) NK cell-induced cytotoxicity is dependent on a Ca2+ increase in the target. FASEB J 4: 2661–2664

    Google Scholar 

  21. Moore K, Cooper SA, Jones DB (1987) Use of the monoclonal antibody WR17 identifying the CD37 gp40–45 Kd antigen complex in the diagnosis of B-lymphoid malignancy. J Pathol 152: 13–21

    Google Scholar 

  22. Robaye B, Mosselmans R, Fiers W, Dumont JE, Galand P (1991) Tumour necrosis factor induces apoptosis (programmed cell death) in normal endothelial cells in vitro. Am J Pathol 138: 447–453

    Google Scholar 

  23. Shi L, Kraut RP, Aebersold R, Greenberg AH (1992) A natural killer cell granule protein that induces DNA fragmentation and apoptosis. J Exp Med 175: 553–556

    Google Scholar 

  24. Stacey NH, Bishop CJ, Halliday JW, Cooksley WGE, Powell LW, Kerr JFR (1985) Apoptosis as the mode of cell death in antibody-dependent lymphocytotoxicity. J Cell Sci 74: 169–179

    Google Scholar 

  25. Stevenson GT, Eady RP, Hough DW, Jurd RD, Stevenson FK (1975) Surface immunoglobulin of guinea-pig leukaemic lymphocytes. Immunology 28: 807–820

    Google Scholar 

  26. Willams GT (1991) Programmed cell death: apoptosis and oncogenesis. Cell 65: 1097–1098

    Google Scholar 

  27. Wyllie AH, Kerr JFR, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68: 251–306

    Google Scholar 

  28. Wyllie AH, Morris RG, Smith AL, Dunlop D (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 142: 67–77

    Google Scholar 

  29. Young JD-E (1989) Killing of target cells by lymphocytes: a mechanistic view. Physiol Rev 69: 250–314

    Google Scholar 

  30. Young JD-E, Cohn ZA, Podack ER (1986) The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological and functional similarities. Science 233: 184–190

    Google Scholar 

  31. Zychlinsky A, Zheng LM, Liu C, Young JD (1991) Cytolytic lymphocytes induce both apoptosis and necrosis in target cells. J Immunol 146: 393–400

    Google Scholar 

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Author notes

  1. S. John Curnow

    Present address: Centre d'immunologie INSERM-CNRS de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, 13 288, Marseille, Cedex 9, France

Authors and Affiliations

  1. Lymphoma Research Unit, Tenovus Laboratory, General Hospital, SO9 4XY, Southampton, UK

    S. John Curnow, Martin J. Glennie & George T. Stevenson

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  1. S. John Curnow
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  2. Martin J. Glennie
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  3. George T. Stevenson
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Curnow, S.J., Glennie, M.J. & Stevenson, G.T. The role of apoptosis in antibody-dependent cellular cytotoxicity. Cancer Immunol Immunother 36, 149–155 (1993). https://doi.org/10.1007/BF01741085

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  • DOI: https://doi.org/10.1007/BF01741085

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