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J Exp Med. 1993 February 1; 177(2): 295–304.
PMCID: PMC2190909

Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10


Interleukin 10 (IL-10) is a pleiotropic factor that enhances proliferation of activated human B lymphocytes and induces them to secrete high amounts of immunoglobulins. Here we show that several human B cell lines were able to constitutively secrete human (h)IL-10. Whereas none of the pre-B nor the plasmocytic cell lines tested produced hIL-10, 25 of the 36 tested mature B cell lines (lymphoblastoid and Burkitt lymphoma cell lines) secreted hIL-10. Moreover, 24 of these 25 hIL-10-producing B cell lines contained the Epstein-Barr virus (EBV) genome, suggesting a relationship between hIL- 10 production by human B cell lines and EBV expression. Accordingly, whereas polyclonal activation via triggering of surface immunoglobulins or CD40 antigen induced highly purified normal human B lymphocytes to produce only low (0.3-0.4 ng/ml) but significant amounts of hIL-10, EBV infection induced them to secrete high amounts of hIL-10 (4-9 ng/ml). Furthermore, addition of exogenous hIL-10, simultaneously to EBV infection, potentiated cell proliferation, whereas a blocking anti-IL- 10 antiserum inhibited it. Thus, hIL-10 produced by infected human B lymphocytes appears to be involved in the mechanisms of EBV-induced B cell proliferation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Banchereau J, Rousset F. Human B lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol. 1992;52:125–262. [PubMed]
  • Bonnefoy JY, Denoroy MC, Guillot O, Martens CL, Banchereau J. Activation of normal human B cells through their antigen receptor induces membrane expression of IL-1 alpha and secretion of IL-1 beta. J Immunol. 1989 Aug 1;143(3):864–869. [PubMed]
  • Smeland EB, Blomhoff HK, Funderud S, Shalaby MR, Espevik T. Interleukin 4 induces selective production of interleukin 6 from normal human B lymphocytes. J Exp Med. 1989 Oct 1;170(4):1463–1468. [PMC free article] [PubMed]
  • Sung SS, Jung LK, Walters JA, Chen W, Wang CY, Fu SM. Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells. J Exp Med. 1988 Nov 1;168(5):1539–1551. [PMC free article] [PubMed]
  • Sung SS, Jung LK, Walters JA, Jeffes EW, 3rd, Granger GA, Fu SM. Production of lymphotoxin by isolated human tonsillar B lymphocytes and B lymphocyte cell lines. J Clin Invest. 1989 Jul;84(1):236–243. [PMC free article] [PubMed]
  • Cairns J, Flores-Romo L, Millsum MJ, Guy GR, Gillis S, Ledbetter JA, Gordon J. Soluble CD23 is released by B lymphocytes cycling in response to interleukin 4 and anti-Bp50 (CDw40). Eur J Immunol. 1988 Mar;18(3):349–353. [PubMed]
  • 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]
  • Paul CC, Keller JR, Armpriester JM, Baumann MA. Epstein-Barr virus transformed B lymphocytes produce interleukin-5. Blood. 1990 Apr 1;75(7):1400–1403. [PubMed]
  • Hutchins D, Cohen BB, Steel CM. Production and regulation of interleukin 6 in human B lymphoid cells. Eur J Immunol. 1990 May;20(5):961–968. [PubMed]
  • Yokoi T, Miyawaki T, Yachie A, Kato K, Kasahara Y, Taniguchi N. Epstein-Barr virus-immortalized B cells produce IL-6 as an autocrine growth factor. Immunology. 1990 May;70(1):100–105. [PubMed]
  • Seregina TM, Mekshenkov MI, Turetskaya RL, Nedospasov SA. An autocrine growth factor constitutively produced by a human lymphoblastoid B-cell line is serologically related to lymphotoxin (TNF-beta). Mol Immunol. 1989 Mar;26(3):339–342. [PubMed]
  • Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. [PMC free article] [PubMed]
  • Suda T, O'Garra A, MacNeil I, Fischer M, Bond MW, Zlotnik A. Identification of a novel thymocyte growth-promoting factor derived from B cell lymphomas. Cell Immunol. 1990 Aug;129(1):228–240. [PubMed]
  • MacNeil IA, Suda T, Moore KW, Mosmann TR, Zlotnik A. IL-10, a novel growth cofactor for mature and immature T cells. J Immunol. 1990 Dec 15;145(12):4167–4173. [PubMed]
  • Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. [PubMed]
  • Vieira P, de Waal-Malefyt R, Dang MN, Johnson KE, Kastelein R, Fiorentino DF, deVries JE, Roncarolo MG, Mosmann TR, Moore KW. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172–1176. [PubMed]
  • Rousset F, Garcia E, Defrance T, Péronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890–1893. [PubMed]
  • Go NF, Castle BE, Barrett R, Kastelein R, Dang W, Mosmann TR, Moore KW, Howard M. Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med. 1990 Dec 1;172(6):1625–1631. [PMC free article] [PubMed]
  • O'Garra A, Stapleton G, Dhar V, Pearce M, Schumacher J, Rugo H, Barbis D, Stall A, Cupp J, Moore K, et al. Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol. 1990;2(9):821–832. [PubMed]
  • Yssel H, De Vries JE, Koken M, Van Blitterswijk W, Spits H. Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J Immunol Methods. 1984 Aug 3;72(1):219–227. [PubMed]
  • Vallé A, Zuber CE, Defrance T, Djossou O, De Rie M, Banchereau J. Activation of human B lymphocytes through CD40 and interleukin 4. Eur J Immunol. 1989 Aug;19(8):1463–1467. [PubMed]
  • Favre C, Wijdenes J, Cabrillat H, Djossou O, Banchereau J, de Vries JE. Epitope mapping of recombinant human gamma interferon using monoclonal antibodies. Mol Immunol. 1989 Jan;26(1):17–25. [PubMed]
  • Peltz GA, Trounstine ML, Moore KW. Cloned and expressed human Fc receptor for IgG mediates anti-CD3-dependent lymphoproliferation. J Immunol. 1988 Sep 15;141(6):1891–1896. [PubMed]
  • Defrance T, Vanbervliet B, Aubry JP, Takebe Y, Arai N, Miyajima A, Yokota T, Lee F, Arai K, de Vries JE, et al. B cell growth-promoting activity of recombinant human interleukin 4. J Immunol. 1987 Aug 15;139(4):1135–1141. [PubMed]
  • Rousset F, Garcia E, Banchereau J. Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J Exp Med. 1991 Mar 1;173(3):705–710. [PMC free article] [PubMed]
  • O'Garra A, Chang R, Go N, Hastings R, Haughton G, Howard M. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur J Immunol. 1992 Mar;22(3):711–717. [PubMed]
  • Calender A, Billaud M, Aubry JP, Banchereau J, Vuillaume M, Lenoir GM. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8060–8064. [PubMed]
  • Benjamin D, Knobloch TJ, Dayton MA. Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. Blood. 1992 Sep 1;80(5):1289–1298. [PubMed]
  • Garner JG, Hirsch MS, Schooley RT. Prevention of Epstein-Barr virus-induced B-cell outgrowth by interferon alpha. Infect Immun. 1984 Mar;43(3):920–924. [PMC free article] [PubMed]
  • Lotz M, Tsoukas CD, Fong S, Carson DA, Vaughan JH. Regulation of Epstein-Barr virus infection by recombinant interferons. Selected sensitivity to interferon-gamma. Eur J Immunol. 1985 May;15(5):520–525. [PubMed]
  • Baumann MA, Paul CC. Interleukin-5 is an autocrine growth factor for Epstein-Barr virus-transformed B lymphocytes. Blood. 1992 Apr 1;79(7):1763–1767. [PubMed]
  • Wakasugi N, Tagaya Y, Wakasugi H, Mitsui A, Maeda M, Yodoi J, Tursz T. Adult T-cell leukemia-derived factor/thioredoxin, produced by both human T-lymphotropic virus type I- and Epstein-Barr virus-transformed lymphocytes, acts as an autocrine growth factor and synergizes with interleukin 1 and interleukin 2. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8282–8286. [PubMed]
  • de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. [PMC free article] [PubMed]
  • Emilie D, Touitou R, Raphael M, Peuchmaur M, Devergnee O, Rea D, Coumbraras J, Crevon MC, Edelman L, Joab I, et al. In vivo production of interleukin-10 by malignant cells in AIDS lymphomas. Eur J Immunol. 1992 Nov;22(11):2937–2942. [PubMed]

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