Is there a role for antigen selection in mantle cell lymphoma? Immunogenetic support from a series of 807 cases

Anastasia Hadzidimitriou, Andreas Agathangelidis, Nikos Darzentas, Fiona Murray, Marie Helene Delfau-Larue, Lone Bredo Pedersen, Alba Navarro Lopez, Antonis Dagklis, Paul Rombout, Kheira Beldjord, Arne Kolstad, Martin H. Dreyling, Achilles Anagnostopoulos, Athanasios Tsaftaris, Penelope Mavragani-Tsipidou, Andreas Rosenwald, Maurilio Ponzoni, Patricia Groenen, Paolo Ghia, Birgitta SanderTheodora Papadaki, Elias Campo, Christian Geisler, Richard Rosenquist, Frederic Davi, Christiane Pott, Kostas Stamatopoulos

Research output: Contribution to journalArticle


We examined 807 productive IGHV-IGHD-IGHJ gene rearrangements from mantle cell lymphoma (MCL) cases, by far the largest series to date. The IGHV gene repertoire was remarkably biased, with IGHV3-21, IGHV4-34, IGHV1-8, and IGHV3-23 accounting for 46.3% of the cohort. Eighty-four of 807 (10.4%) cases, mainly using the IGHV3-21 and IGHV4-34 genes, were found to bear stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences and were placed in 38 clusters. Notably, the MCL stereotypes were distinct from those reported for chronic lymphocytic leukemia. Based on somatic hypermutation (SHM) status, 238/807 sequences (29.5%) carried IGHV genes with 100% germ line identity; the remainder (569/807; 70.5%) exhibited different SHM impact, ranging from minimal (in most cases) to pronounced. Shared replacement mutations across the IGHV gene were identified for certain subgroups, especially those using IGHV3-21, IGHV1-8, and IGHV3-23. Comparison with other entities, in particular CLL, revealed that several of these mutations were "MCL-biased." In conclusion, MCL is characterized by a highly restricted immunoglobulin gene repertoire with stereotyped VH CDR3s and very precise SHM targeting, strongly implying a role for antigen-driven selection of the clonogenic progenitors. Hence, an antigen-driven origin of MCL could be envisaged, at least for subsets of cases.

Original languageEnglish
Pages (from-to)3088-3095
Number of pages8
Issue number11
Publication statusPublished - Sep 15 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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