{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:23:10Z","timestamp":1791235390811,"version":"4.1.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,4,15]]},"abstract":"<jats:p>\n                    To assess the impact of the germinal center (GC) reaction on viral spread in Epstein\u2013Barr virus (EBV) infection, we isolated EBV\n                    <jats:sup>+<\/jats:sup>\n                    GC B cells from the tonsils of two infectious mononucleosis patients, sequenced their rearranged V genes, and determined expression of the EBV latency genes EBV nuclear antigen 2 and latent membrane protein 1. Most EBV\n                    <jats:sup>+<\/jats:sup>\n                    GC B cells belonged to clones of cells harboring somatically mutated V gene rearrangements. Ongoing somatic hypermutation, the hallmark of the GC reaction, was seen only in uninfected GC B cell clones, not in EBV\n                    <jats:sup>+<\/jats:sup>\n                    B cell clones. Thus, in infectious mononucleosis, GC and\/or memory B cells are directly infected by EBV and expand without somatic hypermutation, whereas the GC passage of EBV-infected naive B cells does not contribute detectably to the generation of infected memory B cells, the main reservoir of EBV during persistence. Most, if not all, EBV-infected cells in GCs exhibited an unusual EBV gene expression pattern in that they were positive for EBV nuclear antigen 2 but negative for latent membrane protein 1. Although the three main types of EBV-associated B cell lymphomas (Burkitt's, Hodgkin's, and posttransplant lymphomas) presumably are derived from GC B cells, EBV\n                    <jats:sup>+<\/jats:sup>\n                    GC B cells resembling these EBV\n                    <jats:sup>+<\/jats:sup>\n                    GC B cell lymphomas in terms of EBV gene expression and somatic hypermutation pattern could not be identified.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2627966100","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T18:56:03Z","timestamp":1050432963000},"page":"4730-4735","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":117,"title":["Epstein\u2013Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction"],"prefix":"10.1073","volume":"100","author":[{"given":"Julia","family":"Kurth","sequence":"first","affiliation":[{"name":"Institute for Genetics and Department of Internal Medicine I, University of Cologne, 50931 Cologne, Germany; Department of Pathology, University of Frankfurt, 60590 Frankfurt, Germany; and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin-Leo","family":"Hansmann","sequence":"additional","affiliation":[{"name":"Institute for Genetics and Department of Internal Medicine I, University of Cologne, 50931 Cologne, Germany; Department of Pathology, University of Frankfurt, 60590 Frankfurt, Germany; and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[{"name":"Institute for Genetics and Department of Internal Medicine I, University of Cologne, 50931 Cologne, Germany; Department of Pathology, University of Frankfurt, 60590 Frankfurt, Germany; and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"K\u00fcppers","sequence":"additional","affiliation":[{"name":"Institute for Genetics and Department of Internal Medicine I, University of Cologne, 50931 Cologne, Germany; Department of Pathology, University of Frankfurt, 60590 Frankfurt, Germany; and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,3,28]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"2575","volume-title":"Fields Virology","author":"Rickinson A B","year":"2001","unstructured":"A B Rickinson, E Kieff Fields Virology, eds D M Knipe, P M Howley (Lippincott, Philadelphia), pp. 2575\u20132627 (2001)."},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"6131","DOI":"10.1093\/emboj\/16.20.6131","volume":"16","author":"Gires O","year":"1997","unstructured":"O Gires, U Zimber-Strobl, R Gonnella, M Ueffing, G Marschall, R Zeidler, D Pich, W Hammerschmidt EMBO J 16, 6131\u20136140 (1997).","journal-title":"EMBO J"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S1074-7613(00)80623-8","volume":"9","author":"Caldwell R G","year":"1998","unstructured":"R G Caldwell, J B Wilson, S J Anderson, R Longnecker Immunity 9, 405\u2013411 (1998).","journal-title":"Immunity"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1006\/scbi.2001.0409","volume":"11","author":"Zimber-Strobl U","year":"2001","unstructured":"U Zimber-Strobl, L J Strobl Semin Cancer Biol 11, 423\u2013434 (2001).","journal-title":"Semin Cancer Biol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S1074-7613(00)00049-2","volume":"13","author":"Babcock G J","year":"2000","unstructured":"G J Babcock, D Hochberg, A D Thorley-Lawson Immunity 13, 497\u2013506 (2000).","journal-title":"Immunity"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/381751a0","volume":"381","author":"Rajewsky K","year":"1996","unstructured":"K Rajewsky Nature 381, 751\u2013758 (1996).","journal-title":"Nature"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S1074-7613(00)00048-0","volume":"13","author":"Kurth J","year":"2000","unstructured":"J Kurth, T Spieker, J Wustrow, G J Strickler, L M Hansmann, K Rajewsky, R K\u00fcppers Immunity 13, 485\u2013495 (2000).","journal-title":"Immunity"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1126\/science.286.5438.300","volume":"286","author":"Uchida J","year":"1999","unstructured":"J Uchida, T Yasui, Y Takaoka-Shichijo, M Muraoka, W Kulwichit, N Raab-Traub, H Kikutani Science 286, 300\u2013303 (1999).","journal-title":"Science"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1002\/j.1460-2075.1993.tb06189.x","volume":"12","author":"K\u00fcppers R","year":"1993","unstructured":"R K\u00fcppers, M Zhao, M L Hansmann, K Rajewsky EMBO J 12, 4955\u20134967 (1993).","journal-title":"EMBO J"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1056\/NEJM199911113412007","volume":"341","author":"K\u00fcppers R","year":"1999","unstructured":"R K\u00fcppers, U Klein, M L Hansmann, K Rajewsky N Engl J Med 341, 1520\u20131529 (1999).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1182\/blood.V95.3.1023.003k07_1023_1031","volume":"95","author":"Kanzler H","year":"2000","unstructured":"H Kanzler, R K\u00fcppers, S Helmes, H-H Wacker, A Chott, M-L Hansmann, K Rajewsky Blood 95, 1023\u20131031 (2000).","journal-title":"Blood"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/sj.leu.2402480","volume":"16","author":"K\u00fcppers R","year":"2002","unstructured":"R K\u00fcppers, T Sonoki, E Satterwhite, S Gesk, L Harder, D G Oscier, P W Tucker, M J Dyer, R Siebert Leukemia 16, 937\u2013939 (2002).","journal-title":"Leukemia"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0092-8674(88)90530-2","volume":"52","author":"Lawrence J B","year":"1988","unstructured":"J B Lawrence, C A Villnave, R H Singer Cell 52, 51\u201361 (1988).","journal-title":"Cell"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1002\/1521-4141(200112)31:12<3638::AID-IMMU3638>3.0.CO;2-G","volume":"31","author":"Goossens T","year":"2001","unstructured":"T Goossens, A Br\u00e4uninger, U Klein, R K\u00fcppers, K Rajewsky Eur J Immunol 31, 3638\u20133648 (2001).","journal-title":"Eur J Immunol"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/eji.1830220233","volume":"22","author":"Weiss U","year":"1992","unstructured":"U Weiss, R Zoebelein, K Rajewsky Eur J Immunol 22, 511\u2013517 (1992).","journal-title":"Eur J Immunol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/(SICI)1096-9896(199706)182:2<151::AID-PATH824>3.0.CO;2-3","volume":"182","author":"Niedobitek G","year":"1997","unstructured":"G Niedobitek, A Agathanggelou, H Herbst, L Whitehead, D H Wright, L S Young J Pathol 182, 151\u2013159 (1997).","journal-title":"J Pathol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1182\/blood.V79.10.2520.bloodjournal79102520","volume":"79","author":"Niedobitek G","year":"1992","unstructured":"G Niedobitek, H Herbst, L S Young, L Brooks, J Masucci, A B Crocker, A B Rickinson, H Stein Blood 79, 2520\u20132526 (1992).","journal-title":"Blood"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1182\/blood.V85.3.744.bloodjournal853744","volume":"85","author":"Anagnostopoulos I","year":"1995","unstructured":"I Anagnostopoulos, M Hummel, C Kreschel, H Stein Blood 85, 744\u2013750 (1995).","journal-title":"Blood"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/(SICI)1096-9896(199902)187:3<326::AID-PATH242>3.0.CO;2-N","volume":"187","author":"Araujo I","year":"1999","unstructured":"I Araujo, H-D Foss, M Hummel, I Anagnostopoulos, H S Barbosa, A Bittencourt, H Stein J Pathol 187, 326\u2013330 (1999).","journal-title":"J Pathol"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1182\/blood.V90.4.1664","volume":"90","author":"Niedobitek G","year":"1997","unstructured":"G Niedobitek, E Kremmer, H Herbst, L Whitehead, C W Dawson, E Niedobitek, C von Ostau, N Rooney, F A Grasser, L S Young Blood 90, 1664\u20131672 (1997).","journal-title":"Blood"},{"key":"e_1_3_4_21_2","first-page":"1072","volume":"143","author":"Hamilton-Dutoit S J","year":"1993","unstructured":"S J Hamilton-Dutoit, D Rea, M Raphael, K Sandvej, H J Delecluse, C Gisselbrecht, L Marelle, H J van Krieken, G Pallesen Am J Pathol 143, 1072\u20131085 (1993).","journal-title":"Am J Pathol"},{"key":"e_1_3_4_22_2","first-page":"923","volume":"147","author":"Oudejans J J","year":"1995","unstructured":"J J Oudejans, M Jiwa, A J van den Brule, F A Grasser, A Horstman, W Vos, P M Kluin, P van der Valk, J M Walboomers, C J Meijer Am J Pathol 147, 923\u2013933 (1995).","journal-title":"Am J Pathol"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1126\/science.7537388","volume":"268","author":"Arpin C","year":"1995","unstructured":"C Arpin, J Dechanet, C Van Kooten, P Merville, G Grouard, F Briere, J Banchereau, Y J Liu Science 268, 720\u2013722 (1995).","journal-title":"Science"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/j.1460-2075.1996.tb00367.x","volume":"15","author":"Jochner N","year":"1996","unstructured":"N Jochner, D Eick, U Zimber-Strobl, M Pawlita, G W Bornkamm, B Kempkes EMBO J 15, 375\u2013382 (1996).","journal-title":"EMBO J"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1084\/jem.194.7.927","volume":"194","author":"Br\u00e4uninger A","year":"2001","unstructured":"A Br\u00e4uninger, T Spieker, K Willenbrock, P Gaulard, H H Wacker, K Rajewsky, M L Hansmann, R K\u00fcppers J Exp Med 194, 927\u2013940 (2001).","journal-title":"J Exp Med"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1182\/blood.V85.8.2176.bloodjournal8582176","volume":"85","author":"Chapman C J","year":"1995","unstructured":"C J Chapman, C I Mockridge, M Rowe, A B Rickinson, F K Stevenson Blood 85, 2176\u20132181 (1995).","journal-title":"Blood"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"10488","DOI":"10.1128\/JVI.75.21.10488-10492.2001","volume":"75","author":"Harris R S","year":"2001","unstructured":"R S Harris, D S Croom-Carter, A B Rickinson, M S Neuberger J Virol 75, 10488\u201310492 (2001).","journal-title":"J Virol"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1093\/emboj\/17.6.1700","volume":"17","author":"Kilger E","year":"1998","unstructured":"E Kilger, A Kieser, M Baumann, W Hammerschmidt EMBO J 17, 1700\u20131709 (1998).","journal-title":"EMBO J"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1084\/jem.184.4.1495","volume":"184","author":"Kanzler H","year":"1996","unstructured":"H Kanzler, R K\u00fcppers, M-L Hansmann, K Rajewsky J Exp Med 184, 1495\u20131505 (1996).","journal-title":"J Exp Med"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2627966100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T02:02:23Z","timestamp":1654567343000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2627966100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,28]]},"references-count":29,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2003,4,15]]}},"alternative-id":["10.1073\/pnas.2627966100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2627966100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,28]]},"assertion":[{"value":"2002-12-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}