Abstract
The autocrine growth profile of human B lymphocytes transformed with Epstein-Barr virus (EBV) was found to comprise three distinct components: a B-cell growth factor (BCGF); an interleukin-1 (IL-1)-like activity; an activity requiring cell-to-cell contact for its action. Observations on the inhibition of the EBV-carrying Daudi lymphoma line by α-interferon indicated that loss of response to these autostimulatory factors was underlying growth cessation. Furthermore, a putative for BCGF was found to be down-regulated on B cells stimulated with non-transforming mitogens but constitutively expressed following EBV-transformation. Taken together with recent evidence that normal B cells produce autostimulatory factors, these findings suggest that the special feature of autocrine growth by EBV-immortalized cells is a maintenance of what should normally be a transient phenotype, possibly through deregulation of receptor expression. This hypothesis is discussed.
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Aman P, Gordon J, Lewin N, Nordstöm M, Ehlin-Henriksson B, Klein G, Carstensson A: Surface marker characterization of EBV target cells in normal blood and tonsil B lymphocyte populations.J Immun 135, 2362 (1985).
Walker L, Guy G, Brown G, Milner A, Gordon J: Control of human B-lymphocyte replication. I. Characterization of novel activation stages which precede the entry of G0 B cells into cycle.Immunology 58, 583 (1986).
Gordon J, Walker L, Guy G, Brown G, Rowe M, Rickinson A: Control of human B-lymphocyte replication. II. Transforming Epstein-Barr virus exploits three distinct viral signals to undermine three separate control points in B-cell growth.Immunology 58, 591 (1986).
Blazar B A, Sutton L M, Strome M: Self-stimulating growth factor production by B-cell lines derived from Burkitt's lymphoma and other lines transformedin vitro by Epstein-Barr virus.Cancer Res 43, 4562 (1983).
Gordon J, Ley S C, Melamed M, Aman P, Hughes-Jones N C: Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus.J Exp Med 159, 1554 (1984).
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 cells.J Immun 135, 1132 (1985).
Witzel N, Ambrus J L, Jurgensen C H, Mostowski H, Fauci A S: Production of a monoclonal antibody recognizing a sub-population of human B lymphocytes producing B cell growth factor (BCGF).Fed Proc Abs 4905 (1986).
Gordon J, Melamed M D, Ley S C, English L S, Hughes-Jones N C: Immortalized B lymphocytes produce B-cell growth factor.Nature 310, 145 (1984).
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 IL-1-like activity and an IL-1 inhibitory factor by an EBV-transformed human B-cell line.J Exp Med 159, 1637 (1984).
Gordon J, Guy G, Walker L: Autocrine models of B-lymphocyte growth. II. Interleukin-1 supports the proliferation of transformed lymphoblasts but not the stimulation of resting B cells triggered through their receptors for antigen.Immunology 57, 419 (1986).
Gordon J, Guy G, Walker L: Autocrine models of B-lymphocyte growth. I. Role of cell contact and soluble factors in T-independent B-cell responses.Immunology 56, 329 (1985).
Spicker-Polet H, Hagen K, Teodorescu M: The role of inter-cellular contacts in the activation of B lymphocytes by anti-immunoglobulin antibodies.J Immun 134, 2827 (1985).
Melamed M D, Gordon J, Ley S C, Edgar D, Hughes-Jones N C: Senescence of a human lymphoblastoid clone producing anti-Rhesus (D).Eur J Immun 15, 742 (1985).
Choi J S, Lim K H, Sanders F K: Effect of Interferon on pokeweed mitogen-induced differentiation of human peripheral blood B lymphoctyes.Cellular Immun 64, 20 (1981).
Slovin S F, Frisman D M, Tsoukas C D, Royston I, Baird S M, Wormsley S B, Carson D A, Vaughn J H: Membrane antigen on EBV infected human B cells recognised by a monoclonal antibody.Proc Natl Acad Sci USA 79, 2649 (1982).
Gordon J, Rowe M, Walker L, Guy G: Ligation of the CD23 (BLAST-2, EBVCS) antigen triggers the cell-cycle progression of activated B lymphocytes.Eur J Immunol (in press).
Wang D, Liebawitz D, Kieff K: An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells.Cell 43, 831 (1985).
Thorley-Lawson D A, Mann K P: Early events in EBV infection provide a model for B-cell activation.J Exp Med 162, 45 (1985).
Minegari M C, Geroson F, Moretton A, Zubler R H, Moretta L: B cell growth factor activity of immunoaffinity-purified and recombinant human interleukin 2.Eur J Immunol 15, 193 (1985).
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Gordon, J., Guy, G., Walker, L. et al. Autocrine growth of human blymphocytes: Maintained response to autostimulatory factors is the special feature of immortalization by Epstein-Barr virus—A hypothesis. Med. Oncol. & Tumor Pharmacother. 3, 269–273 (1986). https://doi.org/10.1007/BF02935004
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DOI: https://doi.org/10.1007/BF02935004