Functionally active Epstein-Barr virus-transformed follicular dendritic cell-like cell lines
Abstract
Follicular dendritic cells (FDC) are unique nonlymphoid cells found only in germinal centers. FDC can be distinguished from other accessory cells based on a characteristic set of cell surface markers. It is known that FDC are able to rescue germinal center B cells from apoptosis. To investigate the role of FDC in the process of selection and maturation of B cells during germinal center reactions, we tried to establish factor-independent immortalized FDC-like cell lines. Because freshly isolated FDC express the Epstein-Barr Virus (EBV) receptor CD21, we attempted EBV transformation on isolated FDC. After incubation of FDC-enriched cell populations with EBV, cell lines were obtained consisting of slowly duplicating very large cells. These cell lines have a fibroblast-like morphology but could be clearly distinguished from several human fibroblast cell lines by displaying a different phenotype including intercellular adhesion molecule 1, CD40, and CD75 expression. Detection of the EBV-encoded proteins latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in our FDC-like cell lines implicated successful EBV transformation. FDC-like cells are able to bind nonautologous B cells and preserve the latter from apoptosis. The binding of B cells to FDC-like cells is dependent on adhesion via lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and closely resembles the pattern of emperipolesis as described by others. These data demonstrate that FDC can be successfully infected by EBV, and that the cell lines obtained share phenotypic and functional characteristics with freshly isolated FDC.
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Selected References
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- Gray D, Leanderson T. Expansion, selection and maintenance of memory B-cell clones. Curr Top Microbiol Immunol. 1990;159:1–17. [PubMed] [Google Scholar]
- MacLennan IC, Gray D. Antigen-driven selection of virgin and memory B cells. Immunol Rev. 1986 Jun;91:61–85. [PubMed] [Google Scholar]
- MacLennan IC, Liu YJ, Johnson GD. Maturation and dispersal of B-cell clones during T cell-dependent antibody responses. Immunol Rev. 1992 Apr;126:143–161. [PubMed] [Google Scholar]
- MacLennan IC, Liu YJ, Oldfield S, Zhang J, Lane PJ. The evolution of B-cell clones. Curr Top Microbiol Immunol. 1990;159:37–63. [PubMed] [Google Scholar]
- Gerdes J, Stein H, Mason DY, Ziegler A. Human dendritic reticulum cells of lymphoid follicles: their antigenic profile and their identification as multinucleated giant cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 1983;42(2):161–172. [PubMed] [Google Scholar]
- Heinen E, Lilet-Leclercq C, Mason DY, Stein H, Boniver J, Radoux D, Kinet-Denoël C, Simar LJ. Isolation of follicular dendritic cells from human tonsils and adenoids. II. Immunocytochemical characterization. Eur J Immunol. 1984 Mar;14(3):267–273. [PubMed] [Google Scholar]
- Johnson GD, Hardie DL, Ling NR, Maclennan IC. Human follicular dendritic cells (FDC): a study with monoclonal antibodies (MoAb). Clin Exp Immunol. 1986 Apr;64(1):205–213. [PMC free article] [PubMed] [Google Scholar]
- Parmentier HK, van der Linden JA, Krijnen J, van Wichen DF, Rademakers LH, Bloem AC, Schuurman HJ. Human follicular dendritic cells: isolation and characteristics in situ and in suspension. Scand J Immunol. 1991 Apr;33(4):441–452. [PubMed] [Google Scholar]
- Petrasch S, Perez-Alvarez C, Schmitz J, Kosco M, Brittinger G. Antigenic phenotyping of human follicular dendritic cells isolated from nonmalignant and malignant lymphatic tissue. Eur J Immunol. 1990 May;20(5):1013–1018. [PubMed] [Google Scholar]
- Schnizlein CT, Kosco MH, Szakal AK, Tew JG. Follicular dendritic cells in suspension: identification, enrichment, and initial characterization indicating immune complex trapping and lack of adherence and phagocytic activity. J Immunol. 1985 Mar;134(3):1360–1368. [PubMed] [Google Scholar]
- Schriever F, Freeman G, Nadler LM. Follicular dendritic cells contain a unique gene repertoire demonstrated by single-cell polymerase chain reaction. Blood. 1991 Feb 15;77(4):787–791. [PubMed] [Google Scholar]
- Sellheyer K, Schwarting R, Stein H. Isolation and antigenic profile of follicular dendritic cells. Clin Exp Immunol. 1989 Dec;78(3):431–436. [PMC free article] [PubMed] [Google Scholar]
- Lindhout E, Mevissen ML, Kwekkeboom J, Tager JM, de Groot C. Direct evidence that human follicular dendritic cells (FDC) rescue germinal centre B cells from death by apoptosis. Clin Exp Immunol. 1993 Feb;91(2):330–336. [PMC free article] [PubMed] [Google Scholar]
- Hollowood K, Pease C, Mackay AM, Fletcher CD. Sarcomatoid tumours of lymph nodes showing follicular dendritic cell differentiation. J Pathol. 1991 Mar;163(3):205–216. [PubMed] [Google Scholar]
- Weiss LM, Berry GJ, Dorfman RF, Banks P, Kaiserling E, Curtis J, Rosai J, Warnke RA. Spindle cell neoplasms of lymph nodes of probable reticulum cell lineage. True reticulum cell sarcoma? Am J Surg Pathol. 1990 May;14(5):405–414. [PubMed] [Google Scholar]
- Pallesen G, Myhre-Jensen O. Immunophenotypic analysis of neoplastic cells in follicular dendritic cell sarcoma. Leukemia. 1987 Jul;1(7):549–557. [PubMed] [Google Scholar]
- Clark EA, Grabstein KH, Shu GL. Cultured human follicular dendritic cells. Growth characteristics and interactions with B lymphocytes. J Immunol. 1992 Jun 1;148(11):3327–3335. [PubMed] [Google Scholar]
- Miller G, Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. [PMC free article] [PubMed] [Google Scholar]
- Mevissen ML, Kwekkeboom J, Goormachtig E, Lindhout E, de Groot C. Improvement of EBV transformation and cloning efficiency of human B cells using culture supernatants from lymphoblastoid cell lines. Hum Antibodies Hybridomas. 1993 Apr;4(2):66–73. [PubMed] [Google Scholar]
- Henderson S, Rowe M, Gregory C, Croom-Carter D, Wang F, Longnecker R, Kieff E, Rickinson A. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 1991 Jun 28;65(7):1107–1115. [PubMed] [Google Scholar]
- Young L, Alfieri C, Hennessy K, Evans H, O'Hara C, Anderson KC, Ritz J, Shapiro RS, Rickinson A, Kieff E, et al. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. [PubMed] [Google Scholar]
- Stamenkovic I, Clark EA, Seed B. A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J. 1989 May;8(5):1403–1410. [PMC free article] [PubMed] [Google Scholar]
- Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. [PubMed] [Google Scholar]
- Alés-Martínez JE, Cuende E, Martínez C, Parkhouse RM, Pezzi L, Scott DW. Signalling in B cells. Immunol Today. 1991 Jun;12(6):201–205. [PubMed] [Google Scholar]
- Stamenkovic I, Asheim HC, Deggerdal A, Blomhoff HK, Smeland EB, Funderud S. The B cell antigen CD75 is a cell surface sialytransferase. J Exp Med. 1990 Aug 1;172(2):641–643. [PMC free article] [PubMed] [Google Scholar]
- Munro S, Bast BJ, Colley KJ, Tedder TF. The B lymphocyte surface antigen CD75 is not an alpha-2,6-sialyltransferase but is a carbohydrate antigen, the production of which requires the enzyme. Cell. 1992 Mar 20;68(6):1003–1003. [PubMed] [Google Scholar]
- Stamenkovic I, Sgroi D, Aruffo A. CD22 binds to alpha-2,6-sialyltransferase-dependent epitopes on COS cells. Cell. 1992 Mar 20;68(6):1003–1004. [PubMed] [Google Scholar]
- Bast BJ, Zhou LJ, Freeman GJ, Colley KJ, Ernst TJ, Munro JM, Tedder TF. The HB-6, CDw75, and CD76 differentiation antigens are unique cell-surface carbohydrate determinants generated by the beta-galactoside alpha 2,6-sialyltransferase. J Cell Biol. 1992 Jan;116(2):423–435. [PMC free article] [PubMed] [Google Scholar]
- Tsunoda R, Nakayama M, Heinen E, Miyake K, Suzuki K, Sugai N, Kojima M. Emperipolesis of lymphoid cells by human follicular dendritic cells in vitro. Virchows Arch B Cell Pathol Incl Mol Pathol. 1992;62(2):69–78. [PubMed] [Google Scholar]
- Koopman G, Parmentier HK, Schuurman HJ, Newman W, Meijer CJ, Pals ST. Adhesion of human B cells to follicular dendritic cells involves both the lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and very late antigen 4/vascular cell adhesion molecule 1 pathways. J Exp Med. 1991 Jun 1;173(6):1297–1304. [PMC free article] [PubMed] [Google Scholar]
- Petrasch SG, Kosco MH, Perez-Alvarez CJ, Schmitz J, Brittinger G. Proliferation of germinal center B lymphocytes in vitro by direct membrane contact with follicular dendritic cells. Immunobiology. 1991 Nov;183(5):451–462. [PubMed] [Google Scholar]
- Tanner J, Weis J, Fearon D, Whang Y, Kieff E. Epstein-Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell. 1987 Jul 17;50(2):203–213. [PubMed] [Google Scholar]
- Nemerow GR, Houghten RA, Moore MD, Cooper NR. Identification of an epitope in the major envelope protein of Epstein-Barr virus that mediates viral binding to the B lymphocyte EBV receptor (CR2). Cell. 1989 Feb 10;56(3):369–377. [PubMed] [Google Scholar]
- Birkenbach M, Tong X, Bradbury LE, Tedder TF, Kieff E. Characterization of an Epstein-Barr virus receptor on human epithelial cells. J Exp Med. 1992 Nov 1;176(5):1405–1414. [PMC free article] [PubMed] [Google Scholar]
- Li QX, Young LS, Niedobitek G, Dawson CW, Birkenbach M, Wang F, Rickinson AB. Epstein-Barr virus infection and replication in a human epithelial cell system. Nature. 1992 Mar 26;356(6367):347–350. [PubMed] [Google Scholar]
- Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984 Oct;133(4):1710–1715. [PubMed] [Google Scholar]
- Cormann N, Heinen E, Kinet-Denoel C, Tsunoda R, Simar LJ. Isolation of follicular dendritic cells from human tonsils and adenoids. In vitro culture. Adv Exp Med Biol. 1988;237:171–175. [PubMed] [Google Scholar]
- Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan IC. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. [PubMed] [Google Scholar]
- Mangeney M, Richard Y, Coulaud D, Tursz T, Wiels J. CD77: an antigen of germinal center B cells entering apoptosis. Eur J Immunol. 1991 May;21(5):1131–1140. [PubMed] [Google Scholar]
- Kosco MH, Pflugfelder E, Gray D. Follicular dendritic cell-dependent adhesion and proliferation of B cells in vitro. J Immunol. 1992 Apr 15;148(8):2331–2339. [PubMed] [Google Scholar]
