{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:24:12Z","timestamp":1790857452783,"version":"4.1.0"},"reference-count":59,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,10,1]]},"abstract":"<jats:p>Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a peculiar T cell lymphoma, as expanding B cell clones are often present besides the malignant T cell clones. In addition, large numbers of Epstein-Barr virus (EBV)-infected B cells are frequently observed. To analyze the differentiation status and clonal composition of EBV-harboring B cells in AILD, single EBV-infected cells were micromanipulated from lymph nodes of six patients with frequent EBV+ cells and their rearranged immunoglobulin (Ig) genes analyzed. Most EBV-infected B cells carried mutated Ig genes, indicating that in AILD, EBV preferentially resides in memory and\/or germinal center B cells. EBV+ B cell clones observed in all six cases ranged from small polyclonal to large monoclonal expansions and often showed ongoing somatic hypermutation while EBV\u2212 B cells showed little tendency for clonal expansion. Surprisingly, many members of expanding B cell clones had acquired destructive mutations in originally functional V gene rearrangements and showed an unfavorable high load of replacement mutations in the framework regions, indicating that they accumulated mutations over repeated rounds of mutation and division while not being selected through their antigen receptor. This sustained selection-free accumulation of somatic mutations is unique to AILD. Moreover, the survival and clonal expansion of \u201cforbidden\u201d (i.e., Ig-deficient) B cells has not been observed before in vivo and thus represents a novel type of viral latency in the B cell compartment. It is likely the interplay between the microenvironment in AILD lymph nodes and the viral transformation that leads to the survival and clonal expansion of Ig-less B cells.<\/jats:p>","DOI":"10.1084\/jem.194.7.927","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"927-940","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":96,"title":["Survival and Clonal Expansion of Mutating \u201cForbidden\u201d (Immunoglobulin Receptor\u2013Deficient) Epstein-Barr Virus\u2013Infected B Cells in Angioimmunoblastic T Cell Lymphoma"],"prefix":"10.1084","volume":"194","author":[{"given":"Andreas","family":"Br\u00e4uninger","sequence":"first","affiliation":[{"name":"aDepartment of Pathology, University of Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilmann","family":"Spieker","sequence":"additional","affiliation":[{"name":"aDepartment of Pathology, University of Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Willenbrock","sequence":"additional","affiliation":[{"name":"aDepartment of Pathology, University of Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gaulard","sequence":"additional","affiliation":[{"name":"bDepartment of Pathology, Centre Hospitalier Universitaire Henri Mondor, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Heinrich","family":"Wacker","sequence":"additional","affiliation":[{"name":"cDepartment of Hematopathology, University of Kiel, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[{"name":"dInstitute for Genetics, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin-Leo","family":"Hansmann","sequence":"additional","affiliation":[{"name":"aDepartment of Pathology, University of Frankfurt, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"K\u00fcppers","sequence":"additional","affiliation":[{"name":"dInstitute for Genetics, University of Cologne, 50931 Cologne, Germany"},{"name":"eDepartment of Internal Medicine I, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,10,1]]},"reference":[{"key":"2023072511125884100_R1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/BF00710561","article-title":"Histological, immunohistological and autopsy findings in lymphogranulomatosis X (including angio-immunoblastic lymphadenopathy)","volume":"406","author":"Knecht","year":"1985","journal-title":"Virchows Arch. 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