{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:54:48Z","timestamp":1790006088371,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,6,19]],"date-time":"2002-06-19T00:00:00Z","timestamp":1024444800000},"content-version":"vor","delay-in-days":79,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Mantle cell lymphoma (MCL) is considered to derive from na\u00efve, pregerminal center (GC) CD5<jats:sup>+<\/jats:sup> B\u2010cells. However, the cell of origin has been questioned in recent studies that showed somatic hypermutations in the immunoglobulin (Ig) variable heavy chain (V<jats:sub>H<\/jats:sub>) genes in subsets of MCL. To clarify this issue, we analyzed the IgV<jats:sub>H<\/jats:sub> genes for the presence of somatic hypermutations in 51 MCL cases. Twenty percent of the MCL cases displayed somatically mutated V<jats:sub>H<\/jats:sub> genes (defined as &gt;2% mutated), whereas 80% showed unmutated V<jats:sub>H<\/jats:sub> genes. This finding suggests that MCL is a genetically heterogeneous disease, with the majority of cases originating from unmutated pre\u2010GC B\u2010cells and a subset deriving from more mature B\u2010cells which have been exposed to the GC environment and have undergone somatic hypermutation. A biased V<jats:sub>H<\/jats:sub> gene usage has been demonstrated in several B\u2010cell malignancies; however, this has not yet been investigated in MCL, although V<jats:sub>H<\/jats:sub>4\u201034 overusage has been indicated by small studies. Interestingly, we found a restricted usage of three individual V<jats:sub>H<\/jats:sub> genes in our MCL material; V<jats:sub>H<\/jats:sub>4\u201034 (22%), V<jats:sub>H<\/jats:sub>3\u201021 (16%) and V<jats:sub>H<\/jats:sub>5\u201051 (12%). This novel finding of preferential V<jats:sub>H<\/jats:sub> gene usage in half of the MCL cases may suggest an antigen driven process occurring in B\u2010cells expressing specific V<jats:sub>H<\/jats:sub> genes, thus implicating that Ig specificity could be involved in mantle cell lymphoma development.<\/jats:p>","DOI":"10.1034\/j.1600-0609.2002.01662.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T18:52:56Z","timestamp":1047408776000},"page":"217-224","source":"Crossref","is-referenced-by-count":69,"title":["Somatic hypermutation and V<sub>H<\/sub> gene usage in mantle cell 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