{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:24:06Z","timestamp":1791397446158,"version":"4.3.3"},"reference-count":29,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,8,16]]},"abstract":"<jats:p>When Epstein-Barr virus (EBV) infects B cells in vitro, the result is a proliferating lymphoblast that expresses at least nine latent proteins. It is generally believed that these cells are rigorously controlled in vivo by cytotoxic T cells. Consistent with this, the latently infected cells in the peripheral blood of healthy carriers are not lymphoblasts. Rather, they are resting memory B cells that are probably not subject to direct immunosurveillance by cytotoxic T lymphocytes (CTLs). When patients become immunosuppressed, the viral load increases in the peripheral blood. The expansion of proliferating lymphoblasts due to the suppressed CTL response is believed to account for this increase and is considered to be a major risk factor for posttransplant lymphoproliferative disease (PTLD) and AIDS-associated B cell lymphoma. Here we show that there is an increase in the numbers of latently infected cells in the peripheral blood of immunosuppressed patients. However, the cells are not proliferating lymphoblasts. They are all latently infected, resting, memory B cells\u2014the same population of infected cells found in the blood of healthy carriers. These results are discussed in the context of a model for EBV persistence that explains why PTLD is usually limited to the lymph nodes.<\/jats:p>","DOI":"10.1084\/jem.190.4.567","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"567-576","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":278,"title":["Epstein-Barr Virus\u2013Infected Resting Memory B Cells, Not Proliferating Lymphoblasts, Accumulate in the Peripheral Blood of Immunosuppressed Patients"],"prefix":"10.1084","volume":"190","author":[{"given":"Gregory J.","family":"Babcock","sequence":"first","affiliation":[{"name":"aFrom the Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa L.","family":"Decker","sequence":"additional","affiliation":[{"name":"aFrom the Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Freeman","sequence":"additional","affiliation":[{"name":"bDivision of Transplant Surgery, New England Medical Center Hospitals, Boston, Massachusetts 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Thorley-Lawson","sequence":"additional","affiliation":[{"name":"aFrom the Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,8,16]]},"reference":[{"key":"2023072508495986700_R1","first-page":"2397","article-title":"Epstein-Barr virus","volume-title":"Virology, Vol. 2, 3rd. ed","author":"Rickinson","year":"1996"},{"key":"2023072508495986700_R2","first-page":"2343","article-title":"Epstein-Barr virus and its replication","volume-title":"Virology, Vol. 2, 2nd. ed","author":"Kieff","year":"1996"},{"key":"2023072508495986700_R3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/ijc.2910350107","article-title":"A re-examination of the Epstein-Barr virus carrier state in healthy seropositive individuals","volume":"35","author":"Yao","year":"1985","journal-title":"Int. J. Cancer."},{"key":"2023072508495986700_R4","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1074-7613(00)80493-8","article-title":"Is EBV persistence in vivo a model for B cell homeostasis?","volume":"5","author":"Khan","year":"1996","journal-title":"Immunity."},{"key":"2023072508495986700_R5","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1128\/jvi.70.5.3286-3289.1996","article-title":"Detection of the latent form of Epstein-Barr virus DNA in the peripheral blood of healthy individuals","volume":"70","author":"Decker","year":"1996","journal-title":"J. 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Virol."},{"key":"2023072508495986700_R8","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/0092-8674(95)90513-8","article-title":"A novel form of Epstein-Barr virus latency in normal B cells in vivo","volume":"80","author":"Miyashita","year":"1995","journal-title":"Cell."},{"key":"2023072508495986700_R9","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1128\/jvi.71.7.4882-4891.1997","article-title":"Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell","volume":"71","author":"Miyashita","year":"1997","journal-title":"J. Virol."},{"key":"2023072508495986700_R10","first-page":"207","article-title":"EBV persistence in vivo. 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Lymphoma."},{"key":"2023072508495986700_R15","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1128\/jcm.28.10.2187-2190.1990","article-title":"Detection of Epstein-Barr virus by polymerase chain reaction","volume":"28","author":"Telenti","year":"1990","journal-title":"J. Clin. Microbiol."},{"key":"2023072508495986700_R16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/ijc.2910350108","article-title":"In vitro analysis of the Epstein-Barr virushost balance in long-term renal allograft recipients","volume":"35","author":"Yao","year":"1985","journal-title":"Int. J. Cancer."},{"key":"2023072508495986700_R17","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/ijc.2910390411","article-title":"Characterization of EBV-carrying B-cell populations in healthy seropositive individuals with regard to density, release of transforming virus and spontaneous outgrowth","volume":"39","author":"Lewin","year":"1987","journal-title":"Int. J. 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