Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations

Aliki Xochelli, Vasilis Bikos, Eleftheria Polychronidou, Chrysi Galigalidou, Andreas Agathangelidis, Frédéric Charlotte, Panagiotis Moschonas, Zadie Davis, Monica Colombo, Maria Roumelioti, Lesley Ann Sutton, Patricia Groenen, Michiel van den Brand, Myriam Boudjoghra, Patricia Algara, Alexandra Traverse-Glehen, Ana Ferrer, Evangelia Stalika, Maria Karypidou, George KanellisChristina Kalpadakis, Manuella Mollejo, Gerasimos Pangalis, Panayiotis Vlamos, Rose Marie Amini, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Véronique Giudicelli, Marie Paule Lefranc, Blanca Espinet, Panagiotis Panagiotidis, Miguel Angel Piris, Ming Qing Du, Richard Rosenquist, Theodora Papadaki, Chrysoula Belessi, Manlio Ferrarini, David Oscier, Dimitrios Tzovaras, Paolo Ghia, Frederic Davi, Anastasia Hadzidimitriou, Kostas Stamatopoulos

Research output: Contribution to journalArticlepeer-review

Abstract

The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous (‘public’) heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments.

Original languageEnglish
Pages (from-to)416-421
Number of pages6
JournalJournal of Pathology
Volume247
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

Keywords

  • antigen
  • immunoglobulin gene
  • marginal zone lymphoma
  • ontogeny

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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