{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:36:25Z","timestamp":1791196585079,"version":"4.1.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,1,12]]},"abstract":"<jats:p>\n                    Epstein\u2013Barr virus (EBV) is associated with a variety of human tumors. Although the EBV-infected normal B cells in vitro and the EBV-carrying B cell lymphomas in immunodeficient patients express the full set of latent proteins (type III latency), the majority of EBV-associated malignancies express the restricted type I (EBNA-1 only) or type II (EBNA-1 and LMPs) viral program. The mechanisms responsible for these different latent viral gene expression patterns are only partially known. IL-21 is a potent B cell activator and plasma cell differentiation-inducer cytokine produced by CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. We studied its effect on EBV-carrying B cells. In type I Burkitt lymphoma (BL) cell lines and in the conditional lymphoblastoid cell line (LCL) ER\/EB2-5, IL-21 potently activated STAT3 and induced the expression of LMP-1, but not EBNA-2. The IL-21-treated type I Jijoye M13 BL line ceased to proliferate, and this was paralleled by the induction of IRF4 and the down-regulation of BCL6 expression. In the type III LCLs and BL lines, IL-21 repressed the C-promoter-derived and LMP-2A mRNAs, whereas it up-regulated the expression of LMP-1 mRNAs. The IL-21-treated type III cells underwent plasma cell differentiation with the induction of Blimp-1, and high levels of Ig and Oct-2. IL-21 might be involved in the EBNA-2-independent expression of LMP-1 in EBV-carrying type II cells. In light of the fact that IL-21 is already in clinical trials for the treatment of multiple malignancies, the in vivo modulation of EBV gene expression by IL-21 might have therapeutic benefits for the EBV-carrying malignancies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0912920107","type":"journal-article","created":{"date-parts":[[2009,12,22]],"date-time":"2009-12-22T21:09:29Z","timestamp":1261516169000},"page":"872-877","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":69,"title":["IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter"],"prefix":"10.1073","volume":"107","author":[{"given":"Lor\u00e1nd L.","family":"Kis","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Salamon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma K.","family":"Persson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mi","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc A.","family":"Scheeren","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hergen","family":"Spits","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,12,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1452"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35095584"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210240"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90943-J"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910420305"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19961104)68:3<285::AID-IJC3>3.0.CO;2-Y"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.10.6303-6308.1993"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64168-5"},{"key":"e_1_3_3_9_2","first-page":"923","article-title":"Detection of heterogeneous Epstein-Barr virus gene expression patterns within individual post-transplantation lymphoproliferative disorders","volume":"147","author":"Oudejans JJ","year":"1995","unstructured":"JJ Oudejans, et al., Detection of heterogeneous Epstein-Barr virus gene expression patterns within individual post-transplantation lymphoproliferative disorders. 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