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. 1987 Nov;84(22):8060–8064. doi: 10.1073/pnas.84.22.8060

Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells.

A Calender 1, M Billaud 1, J P Aubry 1, J Banchereau 1, M Vuillaume 1, G M Lenoir 1
PMCID: PMC299477  PMID: 2825176

Abstract

A set of B-cell activation markers, including the EBV/C3d receptor [complement receptor type 2 (CR2) (CD21)], the 45-kDa lymphoblastoid cell-associated (Blast-2) antigen (CD23), and the B-cell restricted activation (Bac-1) antigen (which was recently identified as a potential B-cell growth factor receptor) can be turned on by infecting lymphoma cells that are genome negative for Epstein-Barr virus (EBV) with the B95-8 immortalizing strain of the virus. The nonimmortalizing EBV variant, strain P3HR-1, which possesses a deletion within the BamHI WYH region of the genome containing the coding sequence for the EBV-determined nuclear antigen 2, does not induce expression of these markers. Other lymphoblastoid cell-associated antigen markers can be activated by infection with either immortalizing or nonimmortalizing viruses. These results suggest that the immortalizing potential of EBV is correlated with its ability to induce expression of B-cell activation markers, which are suspected to play a major role in the physiological pathway leading to lymphoid cell proliferation. The viral genomic region deleted in the nonimmortalizing strain of EBV seems to be required for activation of some of these markers. Human lymphoma cell lines, such as those used in this study, can thus help identify the specific EBV genes involved in lymphoid B-cell proliferation and the mechanism of action of these genes.

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Selected References

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  1. Adams A. Concentration of Epstein-Barr virus from cell culture fluids with polyethylene glycol. J Gen Virol. 1973 Sep;20(3):391–394. doi: 10.1099/0022-1317-20-3-391. [DOI] [PubMed] [Google Scholar]
  2. Blazar B. A., Sutton L. M., Strome M. Self-stimulating growth factor production by B-cell lines derived from Burkitt's lymphomas and other lines transformed in vitro by Epstein-Barr virus. Cancer Res. 1983 Oct;43(10):4562–4568. [PubMed] [Google Scholar]
  3. Bornkamm G. W., Hudewentz J., Freese U. K., Zimber U. Deletion of the nontransforming Epstein-Barr virus strain P3HR-1 causes fusion of the large internal repeat to the DSL region. J Virol. 1982 Sep;43(3):952–968. doi: 10.1128/jvi.43.3.952-968.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cheah M. S., Ley T. J., Tronick S. R., Robbins K. C. fgr proto-oncogene mRNA induced in B lymphocytes by Epstein-Barr virus infection. Nature. 1986 Jan 16;319(6050):238–240. doi: 10.1038/319238a0. [DOI] [PubMed] [Google Scholar]
  5. Dambaugh T., Hennessy K., Chamnankit L., Kieff E. U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632–7636. doi: 10.1073/pnas.81.23.7632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fingeroth J. D., Weis J. J., Tedder T. F., Strominger J. L., Biro P. A., Fearon D. T. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4510–4514. doi: 10.1073/pnas.81.14.4510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Frade R., Barel M., Ehlin-Henriksson B., Klein G. gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1490–1493. doi: 10.1073/pnas.82.5.1490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frade R., Crevon M. C., Barel M., Vazquez A., Krikorian L., Charriaut C., Galanaud P. Enhancement of human B cell proliferation by an antibody to the C3d receptor, the gp 140 molecule. Eur J Immunol. 1985 Jan;15(1):73–76. doi: 10.1002/eji.1830150114. [DOI] [PubMed] [Google Scholar]
  9. Gordon J., Aman P., Rosén A., Ernberg I., Ehlin-Henriksson B., Klein G. Capacity of B-lymphocytic lines of diverse tumor origin to produce and respond to B-cell growth factors: a progression model for B-cell lymphomagenesis. Int J Cancer. 1985 Feb 15;35(2):251–256. doi: 10.1002/ijc.2910350218. [DOI] [PubMed] [Google Scholar]
  10. Gordon J., Rowe M., Walker L., Guy G. Ligation of the CD23,p45 (BLAST-2,EBVCS) antigen triggers the cell-cycle progression of activated B lymphocytes. Eur J Immunol. 1986 Sep;16(9):1075–1080. doi: 10.1002/eji.1830160908. [DOI] [PubMed] [Google Scholar]
  11. 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. doi: 10.1126/science.157.3792.1064. [DOI] [PubMed] [Google Scholar]
  12. Kikutani H., Suemura M., Owaki H., Nakamura H., Sato R., Yamasaki K., Barsumian E. L., Hardy R. R., Kishimoto T. Fc epsilon receptor, a specific differentiation marker transiently expressed on mature B cells before isotype switching. J Exp Med. 1986 Nov 1;164(5):1455–1469. doi: 10.1084/jem.164.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. King W., Dambaugh T., Heller M., Dowling J., Kieff E. Epstein-Barr virus DNA XII. A variable region of the Epstein-Barr virus genome is included in the P3HR-1 deletion. J Virol. 1982 Sep;43(3):979–986. doi: 10.1128/jvi.43.3.979-986.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klein G., Ehlin-Henriksson B., Schlossman S. F. Induction of an activated b lymphocyte-associated surface moiety defined by the B2 monoclonal antibody by ebv conversion of an EBV-negative lymphoma line (Ramos): differential effect of transforming (B95-8) and nontransforming (P3HR-1) EBV substrains. J Immunol. 1983 Apr;130(4):1985–1989. [PubMed] [Google Scholar]
  15. Klein G., Lindahl T., Jondal M., Leibold W., Menézes J., Nilsson K., Sundström C. Continuous lymphoid cell lines with characteristics of B cells (bone-marrow-derived), lacking the Epstein-Barr virus genome and derived from three human lymphomas. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3283–3286. doi: 10.1073/pnas.71.8.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klein G., Manneborg A., Steinitz M. Differences in EBV receptor concentration between in vitro EBV-converted lymphoma sublines reflect biological differences between the converting viral substrains. Int J Cancer. 1979 Feb;23(2):197–200. doi: 10.1002/ijc.2910230210. [DOI] [PubMed] [Google Scholar]
  17. Melchers F., Erdei A., Schulz T., Dierich M. P. Growth control of activated, synchronized murine B cells by the C3d fragment of human complement. Nature. 1985 Sep 19;317(6034):264–267. doi: 10.1038/317264a0. [DOI] [PubMed] [Google Scholar]
  18. Miller G., Shope T., Lisco H., Stitt D., Lipman M. Epstein-Barr virus: transformation, cytopathic changes, and viral antigens in squirrel monkey and marmoset leukocytes. Proc Natl Acad Sci U S A. 1972 Feb;69(2):383–387. doi: 10.1073/pnas.69.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mittler R. S., Talle M. A., Carpenter K., Rao P. E., Goldstein G. Generation and characterization of monoclonal antibodies reactive with human B lymphocytes. J Immunol. 1983 Oct;131(4):1754–1761. [PubMed] [Google Scholar]
  20. Nemerow G. R., Siaw M. F., Cooper N. R. Purification of the Epstein-Barr virus/C3d complement receptor of human B lymphocytes: antigenic and functional properties of the purified protein. J Virol. 1986 May;58(2):709–712. doi: 10.1128/jvi.58.2.709-712.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nilsson K., Klein G. Phenotypic and cytogenetic characteristics of human B-lymphoid cell lines and their relevance for the etiology of Burkitt's lymphoma. Adv Cancer Res. 1982;37:319–380. doi: 10.1016/s0065-230x(08)60886-6. [DOI] [PubMed] [Google Scholar]
  22. Pizzo P. A., Magrath I. T., Chattopadhyay S. K., Biggar R. J., Gerber P. A new tumour-derived transforming strain of Epstein-Barr virus. Nature. 1978 Apr 13;272(5654):629–631. doi: 10.1038/272629a0. [DOI] [PubMed] [Google Scholar]
  23. Poncelet P., Carayon P. Cytofluorometric quantification of cell-surface antigens by indirect immunofluorescence using monoclonal antibodies. J Immunol Methods. 1985 Dec 17;85(1):65–74. doi: 10.1016/0022-1759(85)90274-1. [DOI] [PubMed] [Google Scholar]
  24. Reedman B. M., Klein G. Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer. 1973 May;11(3):499–520. doi: 10.1002/ijc.2910110302. [DOI] [PubMed] [Google Scholar]
  25. Ritz J., Pesando J. M., Notis-McConarty J., Lazarus H., Schlossman S. F. A monoclonal antibody to human acute lymphoblastic leukaemia antigen. Nature. 1980 Feb 7;283(5747):583–585. doi: 10.1038/283583a0. [DOI] [PubMed] [Google Scholar]
  26. Rowe D. T., Rowe M., Evan G. I., Wallace L. E., Farrell P. J., Rickinson A. B. Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt's lymphoma cells. EMBO J. 1986 Oct;5(10):2599–2607. doi: 10.1002/j.1460-2075.1986.tb04540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rowe M., Hildreth J. E., Rickinson A. B., Epstein M. A. Monoclonal antibodies to Epstein-Barr virus-induced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T-cell cytotoxicity. Int J Cancer. 1982 Apr 15;29(4):373–381. doi: 10.1002/ijc.2910290403. [DOI] [PubMed] [Google Scholar]
  28. Stein H., Gerdes J., Schwab U., Lemke H., Diehl V., Mason D. Y., Bartels H., Ziegler A. Evidence for the detection of the normal counterpart of Hodgkin and Sternberg-Reed cells. Hematol Oncol. 1983 Jan-Mar;1(1):21–29. doi: 10.1002/hon.2900010105. [DOI] [PubMed] [Google Scholar]
  29. Suzuki T., Sanders S. K., Butler J. L., Gartland G. L., Komiyama K., Cooper M. D. Identification of an early activation antigen (Bac-1) on human B cells. J Immunol. 1986 Aug 15;137(4):1208–1213. [PubMed] [Google Scholar]
  30. Swendeman S., Thorley-Lawson D. A. The activation antigen BLAST-2, when shed, is an autocrine BCGF for normal and transformed B cells. EMBO J. 1987 Jun;6(6):1637–1642. doi: 10.1002/j.1460-2075.1987.tb02412.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thorley-Lawson D. A., Mann K. P. Early events in Epstein-Barr virus infection provide a model for B cell activation. J Exp Med. 1985 Jul 1;162(1):45–59. doi: 10.1084/jem.162.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Thorley-Lawson D. A., Nadler L. M., Bhan A. K., Schooley R. T. BLAST-2 [EBVCS], an early cell surface marker of human B cell activation, is superinduced by Epstein Barr virus. J Immunol. 1985 May;134(5):3007–3012. [PubMed] [Google Scholar]
  33. Thorley-Lawson D. A., Swendeman S. L., Edson C. M. Biochemical analysis suggests distinct functional roles for the BLAST-1 and BLAST-2 antigens. J Immunol. 1986 Mar 1;136(5):1745–1751. [PubMed] [Google Scholar]

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