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High expression of EBNA2 inversely correlated with expression of germinal center (GC)-associated genes, BCL6 and TCL1. The decreased expression of BCL6 appeared to be dose dependent, with almost complete abrogation in highly EBNA2-expressing clones. The role of EBNA2 in negative regulation of these genes was confirmed by transfection and in a hormone-inducible EBNA2 cell system. LMP1 transfection reduced expression of TCL1, but not of BCL6, in DLBCLs. The GC-associated gene repression was at the transcriptional level and CBF1 independent. A decrease in HLA-DR, surface immunoglobulin M, and class II transactivator expression and an increase in CCL3, a BCL6 repression target, was observed in EBNA2-expressing clones. Since BCL6 is indispensable for GC formation and somatic hypermutations (SHM), we suggest that the previously reported lack of SHM seen in EBNA2-expressing GC cells from infectious mononucleosis tonsils could be due to negative regulation of BCL6 by EBNA2. These findings suggest that EBNA2 interferes with the GC phenotype.<\/jats:p>","DOI":"10.1128\/jvi.01822-06","type":"journal-article","created":{"date-parts":[[2006,12,7]],"date-time":"2006-12-07T09:57:14Z","timestamp":1165485434000},"page":"2274-2282","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["EBNA2 Interferes with the Germinal Center Phenotype by Downregulating BCL6 and TCL1 in Non-Hodgkin's Lymphoma Cells"],"prefix":"10.1128","volume":"81","author":[{"given":"Francesco","family":"Boccellato","sequence":"first","affiliation":[{"name":"Istituto Pasteur-Fondazione Cenci-Bolognetti, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Anastasiadou","sequence":"additional","affiliation":[{"name":"Istituto Pasteur-Fondazione Cenci-Bolognetti, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rosato","sequence":"additional","affiliation":[{"name":"Istituto Pasteur-Fondazione Cenci-Bolognetti, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Kempkes","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, GSF National Research Center for Environment and Health, Marchioninistrasse 25, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Frati","sequence":"additional","affiliation":[{"name":"Istituto Pasteur-Fondazione Cenci-Bolognetti, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Faggioni","sequence":"additional","affiliation":[{"name":"Istituto Pasteur-Fondazione Cenci-Bolognetti, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Istituto Pasteur-Fondazione Cenci-Bolognetti, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.3.905"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/1042819021000032917"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1018"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323765"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600509"},{"key":"e_1_3_2_8_2","first-page":"155","volume":"150","year":"1997","unstructured":"Carbone, A., G. 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