Some Recent Trends in Studies of Human Lymphoid Cells: B-Cells, Epstein-Barr Virus, and Transformation

  • J. Zeuthen
  • G. Klein
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 26)


In this brief review we will discuss some recent trends in work on regulatory mechanisms involved in the selective expression of differentiated markers in human B-cell lines as well as the types of controls involved in the expression and function of Epstein-Barr virus (EBV) associated markers in human cells. A problem of special interest in this connection is the relation of the expression of EBV functions to the expression of “transformation”.


Burkitt Lymphoma Ataxia Telangiectasia Somatic Cell Hybrid DAUDI Cell Viral Capsid Antigen 
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  1. Adams A (1979) The state of the virus genome in transformed cells and its relationship to host cell DNA. In: Epstein MA, Achong BG (eds) The Epstein-Barr virus. Springer, Berlin, p 155CrossRefGoogle Scholar
  2. Allan M, Harrison P (1980) Co-expression of differentiation markers in hybrids between Friend cells and lymphoid cells and the influence of cell shape. Cell 19:437PubMedCrossRefGoogle Scholar
  3. Baron D, Strominger JL (1978) Partial purification and properties of the Epstein-Barr virus — associated nuclear antigen. J Biol Chem 253:2875PubMedGoogle Scholar
  4. Béchet JM, Fialkow RJ, Nilsson K, Klein G (1974) Immunoglobulin synthesis and glucose-6-phosphate dehydrogenase as cell markers in human lymphoblastoid cell lines. Exp Cell Res 89:275PubMedCrossRefGoogle Scholar
  5. Ber R, Klein G, Moar M, Povey S, Rosén A, Westman A, Yefenof E, Zeuthen J (1978) Somatic cell hybrids between human lymphoma lines. IV. Establishment and characterization of a P3HR-1/DAUDI hybrid. Int J Cancer 21:707PubMedCrossRefGoogle Scholar
  6. Bernard O, Hozumi N, Tonegawa S (1978) Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell 15:1133PubMedCrossRefGoogle Scholar
  7. Clements GB, Klein G, Povey S (1975) Production by EBV infection of an EBNA-positive subline from an EBNA-negative human lymphoma cell line without detectable EBV DNA. Int J Cancer 16:125PubMedCrossRefGoogle Scholar
  8. Cohen MM, Sagi M, Ben-Zur Z, Schaap T, Voss R, Kohn G (1979) Ataxia telangiectasia: Chromosomal stability in continuous lymphoblastoid cell lines. Cytogenet Cell Genet 23:44PubMedCrossRefGoogle Scholar
  9. Collins SJ, Gallo RC, Gallagher RE (1977) Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature 270:347PubMedCrossRefGoogle Scholar
  10. Einhorn L, Steinitz M, Yefenof E, Ernberg I, Bakacs T, Klein G (1978) Epstein-Barr virus (EBV) receptors complement receptors, and EBV infectability of different lymphocyte fractions of human peripheral blood. II. Epstein-Barr virus studies. Cell Immunol 35:43PubMedCrossRefGoogle Scholar
  11. Epstein MA, Achong BG (1979) Discovery and general biology of the virus. In: Epstein MA, Achong BG (eds) The Epstein-Barr virus. Berlin, Springer, p 1CrossRefGoogle Scholar
  12. Ernberg I, Klein G (1979) EB virus-induced antigens. In: The Epstein MA, Achong BG (eds) The Epstein-Barr virus. Springer, Berlin, p 39CrossRefGoogle Scholar
  13. Eskeland T, Klein E (1971) Isolation of 7S IgM and kappa chains from the surface membrane of tissue culture cells derived from a Burkitt lymphoma. J Immunol 107:1367Google Scholar
  14. Fellous M, Kamoun M, Wiels J, Dausset J, Clements G, Zeuthen J, Klein G (1977) Induction of HLA expression in Daudi cells after cell fusion. Immunogenetics 5:423CrossRefGoogle Scholar
  15. Fialkow PJ, Klein G, Gartier SM, Clifford P (1970) Clonal origin for individual Burkitt tumors. Lancet I;384CrossRefGoogle Scholar
  16. Fialkow PJ, Klein E, Klein G, Clifford P, Singh S (1973) Immunoglobulin and glucose-6-phosphate dehydrogenase as markers of cellular origin in Burkitt lymphoma. J Exp Med 138:89PubMedCrossRefGoogle Scholar
  17. Fresen KO, zur Hausen H (1976) Establishment of EBNA-expressing cell lines by infection of Epstein-Barr virus (EBV)-genome-negative human lymphoma cells with different EBV strains. Int J Cancer 17:161PubMedCrossRefGoogle Scholar
  18. Gergely L, Klein G, Ernberg I (1971) The action of DNA antagonists on Epstein-Barr virus (EBV)-associated early antigens (EA) in Burkitt lymphoma lines. Int J Cancer 7:293PubMedCrossRefGoogle Scholar
  19. Glaser R, Nonoyama M (1973) Epstein-Barr virus: Detection of the genome in somatic cell hybrids of Burkitt lymphoblastoid cells. Science 179:492PubMedCrossRefGoogle Scholar
  20. Glaser R, Rapp F (1972) Rescue of Epstein-Barr virus from somatic cell hybrids of Burkitt lymphoblastoid cells. J Virol 10:288PubMedGoogle Scholar
  21. Glaser R, Ablashi DV, Nonoyama M, Henle W, Easton J (1977) Enhanced oncogenic behavior of human and mouse cells after cellular hybridization with Burkitt tumor cells. Proc Natl Acad Sci USA 74:2574PubMedCrossRefGoogle Scholar
  22. Goodfellow PN, Jones EA, van Heyningen V, Solomon E, Bobrow M, Miggiano V, Bodmer WP (1975) The β2-microglobulin gene is on chromosome 15 and not in the HLA region. Nature 254:267PubMedCrossRefGoogle Scholar
  23. Graessmann A, Graessmann M, Guhl E, Mueller C (1978) Quantitative correlation between simian virus 40 T-antigen synthesis and late viral gene expression in permissive and non-permissive cells. J Cell Biol 77:R1PubMedCrossRefGoogle Scholar
  24. Graessmann A, Wolf H, Bornkamm GW (1980) Expression of Epstein-Barr virus genes in different cell types after microinjection of viral DNA. Proc Natl Acad Sci USA 77:433PubMedCrossRefGoogle Scholar
  25. Hellriegel KP, Diehl V, Krause PH, Meier S, Blankenstein M, Busche W (1977) The significance of chromosomal findings for the differentiation between lymphoma and lymphoblastoid cell lines. In: Thierfelder S, Rodt H, Thiel E (eds) Hematology and blood transfusion. Immunological diagnosis of leukemias and lymphomas. Springer, Berlin, p. 307CrossRefGoogle Scholar
  26. Henle G, Henle W (1979) The virus as the etiologic agent of infectious mononucleosis. In: Epstein MA, Achong BG (eds) The Epstein-Barr virus. Springer, Berlin, p 297CrossRefGoogle Scholar
  27. Jarvis JE, Ball G, Rickinson AB, Epstein MA (1974) Cytogenetic studies on human lymphoblastoid cell lines from Burkitt’s lymphoma and other sources. Int J Cancer 14:716PubMedCrossRefGoogle Scholar
  28. Jondal M, Klein G (1973) Surface markers on human B and T lymphocytes. II. Presence of Epstein-Barr virus (EBV) receptors on B lymphocytes. J Exp Med 138:1365PubMedCrossRefGoogle Scholar
  29. Jondal M, Klein G, Oldstone M, Bokish V, Yefenof E (1976), Surface markers on human B and T lymphocytes. VIII. Association between complement and Epstein-Barr virus (EBV) receptors on human lymphoid cells. Scand J Immunol 5:401PubMedCrossRefGoogle Scholar
  30. Klein G (1979) The relationship of the virus to nasopharyngeal carcinoma. In: Epstein MA, Achong BG (eds) The Epstein-Barr virus. Springer, Berlin, p 339CrossRefGoogle Scholar
  31. Klein E, Eskeland T, Inoue M, Strom R, Johansson B (1970) Surface immunoglobulin moieties on lymphoid cells. Exp Cell Res 62:133PubMedCrossRefGoogle Scholar
  32. Klein G, Wiener F, Zech L, zur Hausen H, Reedman B (1974) Segregation of the EBV-determined nuclear antigen (EBNA) in somatic cell hybrids derived from the fusion of a mouse fibroblast and a human Burkitt line. Int J Cancer 14:54PubMedCrossRefGoogle Scholar
  33. Klein G, Giovanella B, Westman A, Stehlin J, Mumford D (1975) An EBV-genome-negative cell line established from an American Burkitt lymphoma: Receptor characteristics, EBV infectability and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology 5:319PubMedGoogle Scholar
  34. Klein G, Zeuthen J, Terasaki P, Billing R, Honig R, Jondal M, Westman A, Clements G (1976a) Inducibility of the Epstein-Barr virus (EBV) cycle and surface marker properties of EBV-negative lymphoma lines and their in vitro EBV-converted sublines. Int J Cancer 18:639PubMedCrossRefGoogle Scholar
  35. Klein G, Clements G, Zeuthen J, Westman A (1976b) Somatic cell hybrid between human lymphoma lines. II. Spontaneous and induced patterns of the Epstein-Barr virus (EBV) cycle. Int J Cancer 17:71515Google Scholar
  36. Klein G, Terasaki P, Billing R, Honig R, Jondal M, Rosén A, Zeuthen J, Clements G (1977a) Somatic cell hybrids between human lymphoma lines. III. Surface markers. Int J Cancer 19:66PubMedCrossRefGoogle Scholar
  37. Klein G, Clements G, Zeuthen J, Westman A (1977b) Spontaneous and induced patterns of the Epstein-Barr virus (EBV) cycle in a new set of somatic cell hybrids. Cancer Lett 3:91PubMedCrossRefGoogle Scholar
  38. Klein G, Zeuthen J, Eriksson I, Terasaki P, Bernoco M, Rosén A, Masucci G, Povey S, Ber R (1980) Hybridization of a myeloid leukemia — derived human cell line (K562) with a human Burkitt’s lymphoma line (P3HR-1). J Natl Cancer Inst 64:725PubMedGoogle Scholar
  39. Klein G, Luka J, Zeuthen J (1980) Epstein-Barr virus (EBV)-induced transformation and the role of the nuclear antigen (EBNA). Cold Spring Harbor Symp Quant Biol 44:253PubMedGoogle Scholar
  40. Koskimies S (1980) A human lymphoblastoid cell line producing specific antibody against Rh-D antigen. Scand J Immunol 11:73PubMedCrossRefGoogle Scholar
  41. Kozbor D, Steinitz M, Klein G, Koskimies S, Mäkelä O (1979) Establishment of anti-TNP antibody producing human lymphoid lines by preselection for hapten binding followed by EBV transformation. Scand J Immunol 10:187PubMedCrossRefGoogle Scholar
  42. Lenoir G, Bertheion MC, Faure MC, de Thé G (1976) Characterization of Epstein-Barr virus antigens. I. Biochemical analysis of the complement-fixing soluble antigen and relationship with Epstein-Barr virus — associated nuclear antigen. J Virol 17:672PubMedGoogle Scholar
  43. Luka J, Siegert W, Klein G (1977) Solubilization of the Epstein-Barr virus determined nuclear antigen and its characterization as a DNA-binding protein. J Virol 22:1PubMedGoogle Scholar
  44. Luka J, Lindahl T, Klein G (1978) Purification of the Epstein-Barr virus determined nuclear antigen from Epstein-Barr virus transformed human lymphoid cell lines. J Virol 27:604PubMedGoogle Scholar
  45. Luka J, Jörnvall H, Klein G (to be published) Purification and biochemical characterization of the Epstein-Barr virus (EBV) determined nuclear antigen (EBNA) and and an associated protein with a 53K subunit.Google Scholar
  46. Manolov G, Manolova Y (1972) marker band in one chromosome 14 from Burkitt lymphomas. Nature 237:33PubMedCrossRefGoogle Scholar
  47. Matsuoka Y, Takahashi M, Yagi Y, Moore GE, Pressman (1968) Synthesis and secretion of Immunoglobulins by established cell lines of human hematopoietic origin. J Immunol 101:1111PubMedGoogle Scholar
  48. McCaw KB, Hecht F, Harnden DG, Teplitz RJ (1975) Somatic rearrangement of chromosome 14 in human lymphocytes. Proc Natl Acad Sci USA 72:2071PubMedCrossRefGoogle Scholar
  49. McConnell I, Klein G, Lint TF, Lachmann PJ (1978) Activation of the alternative complement pathway by human B cell lymphoma lines is associated with Epstein-Barr virus transformation of the cells. Eur J. Immunol 8:453Google Scholar
  50. McCormick F, Harlow E (1980) Association of a murine 53,000-daltonphosphoprotein with simian virus 40 large-T antigen in transformed cells. J Virol 34:213PubMedGoogle Scholar
  51. Menezes J, Leibold W, Klein G, Clements G (1975) Establishment of an Epstein-Barr virus (EBV)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt’s lymphoma. Biomedicine 22:276PubMedGoogle Scholar
  52. Moar MH, Ber R, Klein G, Westman A, Eriksson I (1978) Somatic cell hybrids between human lymphoma lines. V. IUdR inducibility and P3HR-1 superinfectability of Daudi/HeLa (DAD) and Daudi/P3HR-1 (DIP-1) cell lines. Int J Cancer 22:669PubMedCrossRefGoogle Scholar
  53. Montagnier L, Gruest J (1979) Cell-density-dependence for growth in agarose of two human lymphoma lines and its decrease after Epstein-Barr virus conversion. Int J Cancer 23:71PubMedCrossRefGoogle Scholar
  54. Nilsson K (1978) Established human lymphoid cell lines as models for B-lymphocyte differentiation. In: Serrou B, Rosenfeld C (eds) Human lymphocyte differentiation: Its application to cancer. North-Holland, Amsterdam, p 307Google Scholar
  55. Nilsson K, Pontén J (1975) Classification and biological nature of established human hematopoietic cell lines. Int J Cancer 15:321PubMedCrossRefGoogle Scholar
  56. Nilsson K, Giovanella BC, Stehlin JS, Klein G (1977) Tumorigenicity of human hematopoietic cell lines in athymic nude mice. Int J Cancer 19:337PubMedCrossRefGoogle Scholar
  57. Nyormoi O, Klein G, Adams A, Dombos L (1973) Sensitivity to EBV superinfection and IUdR inducibility of hybrid cells formed between a sensitive and a relatively resistant Burkitt lymphoma cell line. Int J Cancer 12:396PubMedCrossRefGoogle Scholar
  58. Oliver N, Francke U, Pellegrino MA (1978) Regional assignment of genes for mannose phosphate isomerase, pyruvate kinase 3, and β2-microglobulin expression on human chromosome 15 by hybridization of cells from a t(15;22) (q14;q13.3) translocation carrier. Cytogenet Cell Genet 22:506PubMedCrossRefGoogle Scholar
  59. Plesner T (1978) Lymphocyte associated β2-microglobulin studied by crossed radioimmunoelectrophoresis. Scand J Immunol 8:363PubMedCrossRefGoogle Scholar
  60. Pope JH (1979) Transformation by the virus in vitro. In: Epstein MA, Achong BG (eds) The Epstein-Barr virus. Springer, Berlin p 205CrossRefGoogle Scholar
  61. Povey S, Jeremiah S, Arthur E, Ber R, Fialkow PJ, Gardiner E, Goodfellow PN, Karande A, Quintero M, Steel CM, Zeuthen J (to be published) Deficiency of malic enzyme: A possible marker for malignancy in lymphoid cells Ann Hum GenetGoogle Scholar
  62. Reedman B, Klein G (1973) Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer 11:499PubMedCrossRefGoogle Scholar
  63. Rosén A, Clements G, Klein G, Zeuthen J (1977) Double Immunoglobulin production in cloned somatic cell hybrids between two human lymphoid lines. Cell 11:139PubMedCrossRefGoogle Scholar
  64. Rutherford TR, Clegg JB, Weatherall DJ (1979) K562 human leukaemic cells synthesize embryonic haemoglobin in response to haemin. Nature 280:164PubMedCrossRefGoogle Scholar
  65. Singer PA, Williamson AR (1979) A novel interaction involving a Polypeptide chain (P33) in covalent linkage with IgM on the surface of a Burkitt lymphoma cell line (Daudi). Eur J Immunol 9:224PubMedCrossRefGoogle Scholar
  66. Steel CM, Woodward MA, Davidson C, Philipson J, Arthur E (1977) Non-random chromosome gains in human lymphoblastoid cell lines. Nature 270:349PubMedCrossRefGoogle Scholar
  67. Steinitz M, Klein G (1975) Comparison between growth characteristics of an Epstein-Barr virus (EBV)-genome negative lymphoma line and its EBV-converted subline in vitro. Proc Natl Acad Sci USA 72:3518PubMedCrossRefGoogle Scholar
  68. Steinitz M, Klein G (1976) Epstein-Barr virus (EBV)-induced change in saturation density and serum dependence of established, EBV-negative lymphoma lines in vitro. Virology 70:570PubMedCrossRefGoogle Scholar
  69. Steinitz M, Klein G (1977) Further studies on the differences in serum dependence in EBV-negative lymphoma lines and their in vitro converted, virusgenome carrying sublines. Eur J Cancer 13:1269PubMedGoogle Scholar
  70. Steinitz M, Klein G, Koskimies S, Mäkelä O (1977) EB virus-induced B-lymphocyte cell lines producing specific antibody. Nature 269:420PubMedCrossRefGoogle Scholar
  71. Steinitz M, Koskimies S, Klein G, Mäkelä O (1978) Establishment of specific antibody producing human cell lines by antigen preselection and EBV transformation. Curr Top Microbiol Immunol 81:156PubMedGoogle Scholar
  72. Steinitz M, Seppälä I, Klein G, Koskimies S, Mäkelä O (1979) Immunobiology 156:41PubMedGoogle Scholar
  73. Steinitz M, Izak G, Cohen S, Ehrenfeld M, Flechner J (to be published) Continuous production of rheumatoid factor by in vitro EBV-transformed lymphocytes. NatureGoogle Scholar
  74. Tanaka A, Nonoyama M, Glaser R (1977) Transcription of latent Epstein-Barr virus genomes in human epithelial/Burkitt hybrid cells. Virology 82:63PubMedCrossRefGoogle Scholar
  75. Tjian R, Fey G, Graessmann A (1978) Biological activity of purified simian virus 40 T antigen proteins. Proc Natl Acad Sci USA 75:1279PubMedCrossRefGoogle Scholar
  76. Van den Berghe, H, Parloir C, Gosseye S, Englebienne V, Cornu G, Sokal G (1979) Variant translocation in Burkitt lymphoma Cancer Genet Cytogenet 1:9Google Scholar
  77. Van Furth R, Gorter H, Nadkarni JS, Klein E, Clifford P (1972) Synthesis of Immunoglobulins by biopsied tissues and cell lines from Burkitt’s lymphoma. Immunology 22:847PubMedGoogle Scholar
  78. Yefenof E, Klein G (1976) Difference in antibody induced redistribution of membrane IgM in EBV-genome free and EBV-positive human lymphoid cells. Exp Cell Res 99:175PubMedCrossRefGoogle Scholar
  79. Yefenof E, Klein G, Ben-Bassat H, Lundin L (1977) Differences in the ConA-induced redistribution and agglutination patterns of EBV genome-free and EBV-carrying human lymphoma lines. Exp Cell Res 108:185PubMedGoogle Scholar
  80. Zech L, Haglund U, Nilsson K, Klein G (1976) Characteristic chromosomal abnormalities in biopsies and lymphoid cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer 17:47PubMedCrossRefGoogle Scholar
  81. Zeuthen J, Nilsson K (1976) Hybridization of a human myeloma permanent cell line with mouse cells. Cell Differ 4:355PubMedCrossRefGoogle Scholar
  82. Zeuthen J, Friedrich U, Rosén A, Klein E (1977) Structural abnormalities in chromosome 15 in cell lines with reduced expression of Beta-2 microglobulin. Immunogenetics 4:567CrossRefGoogle Scholar
  83. Zeuthen J, Klein G, Ber R, Masucci G, Bisballe S, Povey S, Terasaki P, Ralph P (to be published) Human lymphoma/lymphoma and lymphoma/leukemia hybrids. I. Isolation, characterization, cell surface and B-cell marker studies. J Natl Cancer InstGoogle Scholar
  84. Zur Hausen H, Bornkamm GW, Schmidt R, Hecker E (1979) Tumor initiators and promotors in the induction of Epstein-Barr virus. Proc Natl Acad Sci USA 76:782PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1981

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  • J. Zeuthen
  • G. Klein

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