Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1990 Apr;80(1):62–68. doi: 10.1111/j.1365-2249.1990.tb06442.x

Induction of B cell responsiveness to growth factors by Epstein-Barr virus conversion: comparison of endogenous factors and interleukin-1.

B A Blazar 1, A M Murphy 1
PMCID: PMC1535234  PMID: 2157568

Abstract

Immortalized B lymphocytes produce a factor(s) that stimulates growth of B cell lines carrying Epstein-Barr virus (EBV). Stimulatory supernatants derived from B cells also exhibit interleukin-1 (IL-1) activity in costimulator assays with the D10.G4.1 helper T cell line. Experiments with purified macrophage-derived IL-1 and recombinant IL-1 beta demonstrate that IL-1 stimulates proliferation of the cell lines that respond to the factors from B lymphocyte lines. One B cell line, Ramos, an EBV-Burkitt's lymphoma, contrasts with other B cell lines in that it is refractory to the growth enhancing effects of B cell conditioned medium and macrophage-derived IL-1. When EBV was introduced into Ramos cells, growth was enhanced by the factor(s) in B cell conditioned medium (six out of seven lines); growth of EBV-converted Ramos lines (six out of seven lines) also was enhanced by IL-1. These findings demonstrate that infection of a non-responsive transformed B lymphocyte by EBV induces cellular responsiveness to factor-mediated growth stimulation.

Full text

PDF
62

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambrus J. L., Jr, Jurgensen C. H., Brown E. J., Fauci A. S. Purification to homogeneity of a high molecular weight human B cell growth factor; demonstration of specific binding to activated B cells; and development of a monoclonal antibody to the factor. J Exp Med. 1985 Oct 1;162(4):1319–1335. doi: 10.1084/jem.162.4.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blazar B. A., Sutton L. M., Strome M. Immunomodulating activity in supernatants from EBV immortalized lymphocytes. Cancer Immunol Immunother. 1986;22(1):62–67. doi: 10.1007/BF00205718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Buck J., Hämmerling U., Hoffmann M. K., Levi E., Welte K. Purification and biochemical characterization of a human autocrine growth factor produced by Epstein-Barr virus-transformed B cells. J Immunol. 1987 May 1;138(9):2923–2928. [PubMed] [Google Scholar]
  5. Chu E., Rosenwasser L. J., Dinarello C. A., Lareau M., Geha R. S. Role of interleukin 1 in antigen-specific T cell proliferation. J Immunol. 1984 Mar;132(3):1311–1316. [PubMed] [Google Scholar]
  6. Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
  7. Ernberg I., Klein G., Giovanella B. C., Stehlin J., McCormick K. J., Andersson-Anvret M., Aman P., Killander D. Relationship between the amounts of EBV-DNA and EBNA per cell, clonability and tumorigenicity in two ebv-negative lymphoma lines and their EBV-converted sublines. Int J Cancer. 1983 Feb 15;31(2):163–169. doi: 10.1002/ijc.2910310206. [DOI] [PubMed] [Google Scholar]
  8. Falkoff R. J., Muraguchi A., Hong J. X., Butler J. L., Dinarello C. A., Fauci A. S. The effects of interleukin 1 on human B cell activation and proliferation. J Immunol. 1983 Aug;131(2):801–805. [PubMed] [Google Scholar]
  9. Fresen K. O., Hausen H. 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. 1976 Feb 15;17(2):161–166. doi: 10.1002/ijc.2910170203. [DOI] [PubMed] [Google Scholar]
  10. Gerrard T. L., Volkman D. J. IL 1-like activity in antigen-presenting human B cell lines. J Immunol. 1985 Nov;135(5):3217–3223. [PubMed] [Google Scholar]
  11. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gordon J., Ley S. C., Melamed M. D., Aman P., Hughes-Jones N. C. Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus. J Exp Med. 1984 May 1;159(5):1554–1559. doi: 10.1084/jem.159.5.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gordon J., Ley S. C., Melamed M. D., English L. S., Hughes-Jones N. C. Immortalized B lymphocytes produce B-cell growth factor. Nature. 1984 Jul 12;310(5973):145–147. doi: 10.1038/310145a0. [DOI] [PubMed] [Google Scholar]
  14. Howard M., Mizel S. B., Lachman L., Ansel J., Johnson B., Paul W. E. Role of interleukin 1 in anti-immunoglobulin-induced B cell proliferation. J Exp Med. 1983 May 1;157(5):1529–1543. doi: 10.1084/jem.157.5.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Issekutz T., Chu E., Geha R. S. Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells. J Immunol. 1982 Oct;129(4):1446–1450. [PubMed] [Google Scholar]
  16. Jurgensen C. H., Ambrus J. L., Jr, Fauci A. S. Production of B cell growth factor by normal human B cells. J Immunol. 1986 Jun 15;136(12):4542–4547. [PubMed] [Google Scholar]
  17. Klein E., Klein G., Nadkarni J. S., Nadkarni J. J., Wigzell H., Clifford P. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res. 1968 Jul;28(7):1300–1310. [PubMed] [Google Scholar]
  18. Klein G., Dombos L., Gothoskar B. Sensitivity of Epstein-Barr virus (EBV) producer and non-producer human lymphoblastoid cell lines to superinfection with EB-virus. Int J Cancer. 1972 Jul 15;10(1):44–57. doi: 10.1002/ijc.2910100108. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Klein G., Giovanella B., Westman A., Stehlin J. S., Mumford D. An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology. 1975;5(6):319–334. doi: 10.1159/000149930. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Klein G., Zeuthen J., Terasaki P., Billing R., Honig R., Jondal M., Westman A., Clements G. 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. 1976 Nov 15;18(5):639–652. doi: 10.1002/ijc.2910180513. [DOI] [PubMed] [Google Scholar]
  23. Kurt-Jones E. A., Beller D. I., Mizel S. B., Unanue E. R. Identification of a membrane-associated interleukin 1 in macrophages. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1204–1208. doi: 10.1073/pnas.82.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kurt-Jones E. A., Kiely J. M., Unanue E. R. Conditions required for expression of membrane IL 1 on B cells. J Immunol. 1985 Sep;135(3):1548–1550. [PubMed] [Google Scholar]
  25. Lipsky P. E., Thompson P. A., Rosenwasser L. J., Dinarello C. A. The role of interleukin 1 in human B cell activation: inhibition of B cell proliferation and the generation of immunoglobulin-secreting cells by an antibody against human leukocytic pyrogen. J Immunol. 1983 Jun;130(6):2708–2714. [PubMed] [Google Scholar]
  26. Matsushima K., Kuang Y. D., Tosato G., Hopkins S. J., Oppenheim J. J. B-cell-derived interleukin 1 (IL-1)-like factor. I. Relationship of production of IL-1-like factor to accessory cell function of Epstein-Barr virus-transformed human B-lymphoblast lines. Cell Immunol. 1985 Sep;94(2):406–417. doi: 10.1016/0008-8749(85)90264-3. [DOI] [PubMed] [Google Scholar]
  27. Matsushima K., Procopio A., Abe H., Scala G., Ortaldo J. R., Oppenheim J. J. Production of interleukin 1 activity by normal human peripheral blood B lymphocytes. J Immunol. 1985 Aug;135(2):1132–1136. [PubMed] [Google Scholar]
  28. Menezes J., Leibold W., Klein G. Biological differences between Epstein-Barr virus (EBV) strains with regard to lymphocyte transforming ability, superinfection and antigen induction. Exp Cell Res. 1975 May;92(2):478–484. doi: 10.1016/0014-4827(75)90404-8. [DOI] [PubMed] [Google Scholar]
  29. Mizel S. B. Interleukin 1 and T cell activation. Immunol Rev. 1982;63:51–72. doi: 10.1111/j.1600-065x.1982.tb00411.x. [DOI] [PubMed] [Google Scholar]
  30. Muraguchi A., Nishimoto H., Kawamura N., Hori A., Kishimoto T. B cell-derived BCGF functions as autocrine growth factor(s) in normal and transformed B lymphocytes. J Immunol. 1986 Jul 1;137(1):179–186. [PubMed] [Google Scholar]
  31. Pistoia V., Cozzolino F., Rubartelli A., Torcia M., Roncella S., Ferrarini M. In vitro production of interleukin 1 by normal and malignant human B lymphocytes. J Immunol. 1986 Mar 1;136(5):1688–1692. [PubMed] [Google Scholar]
  32. 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]
  33. Rimsky L., Wakasugi H., Ferrara P., Robin P., Capdevielle J., Tursz T., Fradelizi D., Bertoglio J. Purification to homogeneity and NH2-terminal amino acid sequence of a novel interleukin 1 species derived from a human B cell line. J Immunol. 1986 May 1;136(9):3304–3310. [PubMed] [Google Scholar]
  34. Scala G., Kuang Y. D., Hall R. E., Muchmore A. V., Oppenheim J. J. Accessory cell function of human B cells. I. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line. J Exp Med. 1984 Jun 1;159(6):1637–1652. doi: 10.1084/jem.159.6.1637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Spira G., Aman P., Koide N., Lundin G., Klein G., Hall K. Cell-surface immunoglobulin and insulin receptor expression in an EBV-negative lymphoma cell line and its EBV-converted sublines. J Immunol. 1981 Jan;126(1):122–126. [PubMed] [Google Scholar]
  37. Steinitz M., Klein G. 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 U S A. 1975 Sep;72(9):3518–3520. doi: 10.1073/pnas.72.9.3518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Steinitz M., Klein G. Further studies on the differences in serum dependence in EBV negative lymphoma lines and their in vitro EBV converted, virus-genome carrying sublines. Eur J Cancer. 1977 Nov;13(11):1269–1275. doi: 10.1016/0014-2964(77)90035-4. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Uchibayashi N., Kikutani H., Barsumian E. L., Hauptmann R., Schneider F. J., Schwendenwein R., Sommergruber W., Spevak W., Maurer-Fogy I., Suemura M. Recombinant soluble Fc epsilon receptor II (Fc epsilon RII/CD23) has IgE binding activity but no B cell growth promoting activity. J Immunol. 1989 Jun 1;142(11):3901–3908. [PubMed] [Google Scholar]
  41. Wang F., Gregory C. D., Rowe M., Rickinson A. B., Wang D., Birkenbach M., Kikutani H., Kishimoto T., Kieff E. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23. Proc Natl Acad Sci U S A. 1987 May;84(10):3452–3456. doi: 10.1073/pnas.84.10.3452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yukawa K., Kikutani H., Owaki H., Yamasaki K., Yokota A., Nakamura H., Barsumian E. L., Hardy R. R., Suemura M., Kishimoto T. A B cell-specific differentiation antigen, CD23, is a receptor for IgE (Fc epsilon R) on lymphocytes. J Immunol. 1987 Apr 15;138(8):2576–2580. [PubMed] [Google Scholar]
  43. Ziegler K., Unanue E. R. Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes. J Immunol. 1981 Nov;127(5):1869–1875. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES