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Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece.
Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.
CERTH, Informat Technol Inst, Thessaloniki, Greece;Ionian Univ, Dept Informat, Corfu, Greece.
CERTH, Inst Appl Biosci, Thessaloniki, Greece.
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2019 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 247, no 4, p. 416-421Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 247, no 4, p. 416-421
Keywords [en]
marginal zone lymphoma, ontogeny, immunoglobulin gene, antigen
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-379880DOI: 10.1002/path.5209ISI: 000460465000003PubMedID: 30484876OAI: oai:DiVA.org:uu-379880DiVA, id: diva2:1299361
Funder
EU, Horizon 2020, 692298EU, Horizon 2020, LQ1601Swedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg FoundationErik, Karin och Gösta Selanders FoundationAvailable from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-03-29Bibliographically approved

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Xochelli, AlikiAmini, Rose-MarieStamatopoulos, Kostas

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