{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:52:16Z","timestamp":1791355936376,"version":"4.3.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,9,29]]},"abstract":"<jats:p>\n                    The molecular mechanism involved in the process of antigen-driven somatic hypermutation of Ig genes is unknown, but it is commonly believed that this mechanism is restricted to the Ig loci. B cell lymphomas commonly display multiple somatic mutations clustering in the 5\u2032-regulatory region of BCL-6, a proto-oncogene encoding for a POZ\/Zinc finger transcriptional repressor expressed in germinal center (GC) B cells and required for GC formation. To determine whether BCL-6 mutations represent a tumor-associated phenomenon or reflect a physiologic mechanism, we screened single human tonsillar GC B cells for mutations occurring in the BCL-6 5\u2032-noncoding region and in the Ig variable heavy chain sequences. Thirty percent of GC B cells, but not naive B cells, displayed mutations in the 742 bp region analyzed within the first intron of BCL-6 (overall frequency: 5 \u00d7 10\n                    <jats:sup>\u22124<\/jats:sup>\n                    \/bp). Accordingly, an expanded survey in lymphoid malignancies showed that BCL-6 mutations are restricted to B cell tumors displaying GC or post-GC phenotype and carrying mutated Ig variable heavy chain sequences. These results indicate that the somatic hypermutation mechanism active in GC B cells physiologically targets non-Ig sequences.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.20.11816","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"11816-11821","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":428,"title":["BCL-6 mutations in normal germinal center B cells: Evidence of somatic hypermutation acting outside Ig loci"],"prefix":"10.1073","volume":"95","author":[{"given":"Laura","family":"Pasqualucci","sequence":"first","affiliation":[{"name":"Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032; Servizio di Ematologia, Istituto di Scienze Mediche, Universita\u2019 di Milano, Ospedale Maggiore Istituto di Ricoveroe Cura a Carattere Scientifico, Milan 20122, Italy; Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Institute of Genetics, University of Cologne, Cologne 50931, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Migliazza","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032; Servizio di Ematologia, Istituto di Scienze Mediche, Universita\u2019 di Milano, Ospedale Maggiore Istituto di Ricoveroe Cura a Carattere Scientifico, Milan 20122, Italy; Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Institute of Genetics, University of Cologne, Cologne 50931, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Fracchiolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"William","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032; Servizio di Ematologia, Istituto di Scienze Mediche, Universita\u2019 di Milano, Ospedale Maggiore Istituto di Ricoveroe Cura a Carattere Scientifico, Milan 20122, Italy; Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Institute of Genetics, University of Cologne, Cologne 50931, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Baldini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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Servizio di Ematologia, Istituto di Scienze Mediche, Universita\u2019 di Milano, Ospedale Maggiore Istituto di Ricoveroe Cura a Carattere Scientifico, Milan 20122, Italy; Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Institute of Genetics, University of Cologne, Cologne 50931, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032; Servizio di Ematologia, Istituto di Scienze Mediche, Universita\u2019 di Milano, Ospedale Maggiore Istituto di Ricoveroe Cura a Carattere Scientifico, Milan 20122, Italy; Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Institute of Genetics, University of Cologne, Cologne 50931, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Dalla-Favera","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032; 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