Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations
Aliki Xochelli
(1, 2)
,
Vasilis Bikos
(3)
,
Eleftheria Polychronidou
(2)
,
Chrysi Galigalidou
(2)
,
Andreas C Agathangelidis
(4)
,
Frédéric Charlotte
(5)
,
Panagiotis Moschonas
(2)
,
Zadie Davi
,
Monica Colombo
(6)
,
Maria Roumelioti
(7)
,
Lesley-Ann Sutton
(8, 9)
,
Patricia Groenen
(10)
,
Michiel van den Brand
(10)
,
Myriam C Boudjoghra
(11, 5)
,
Patricia Algara
(12)
,
Alexandra Traverse-Glehen
(13)
,
Ana Juan Ferrer
,
Evangelia C Stalika
(2)
,
Maria Karypidou
(14)
,
George Kanellis
(15)
,
Christina Kalpadakis
(16)
,
Manuella Mollejo
(12)
,
Gerasimos Pangalis
(14)
,
Panayiotis Vlamos
(17)
,
Rose-Marie Amini
(1)
,
Sarka C Pospisilova
(3)
,
Maurilio Ponzoni
(18)
,
Achilles Anagnostopoulos
(14)
,
Véronique Giudicelli
(19)
,
Marie-Paule Lefranc
(19)
,
Blanca Espinet
,
Panagiotis F Panagiotidis
(7)
,
Miguel Angel Piris
,
Ming-Qing Du
(20)
,
Richard Rosenquist
(8)
,
Theodora Papadaki
(15)
,
Chrysoula C Belessi
,
Manlio Ferrarini
(21)
,
David Oscier
,
Dimitrios Tzovaras
(22)
,
Paolo C Ghia
(4)
,
Frederic Davi
(5)
,
Anastasia C Hadzidimitriou
(2)
,
Kostas C Stamatopoulos
(23, 8)
1
Uppsala University
2 CERTH - Centre for Research and Technology Hellas
3 CEITEC MU - Central European Institute of Technology [Brno]
4 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
5 CHU Pitié-Salpêtrière [AP-HP]
6 Ospedale Policlinico San Martino [Genoa]
7 NTUA - National Technical University of Athens [Athens]
8 Uppsala Universitet [Uppsala]
9 Karolinska Institutet [Stockholm]
10 Radboud University Medical Center [Nijmegen]
11 UPMC - Université Pierre et Marie Curie - Paris 6
12 Hospital Virgen de la Salud
13 HCL - Hospices Civils de Lyon
14 General Hospital of Thessaloniki George Papanikolaou
15 Evangelismos Athens General Hospital
16 UOC - University of Crete [Heraklion]
17 Department of Informatics [Ionian University]
18 IRCCS San Raffaele Scientific Institute [Milan, Italie]
19 IGH - Institut de génétique humaine
20 CAM - University of Cambridge [UK]
21 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
22 ITI - Informatics & Telematics Institute
23 CERTH - Centre for Research and Technology Hellas [Athènes]
2 CERTH - Centre for Research and Technology Hellas
3 CEITEC MU - Central European Institute of Technology [Brno]
4 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
5 CHU Pitié-Salpêtrière [AP-HP]
6 Ospedale Policlinico San Martino [Genoa]
7 NTUA - National Technical University of Athens [Athens]
8 Uppsala Universitet [Uppsala]
9 Karolinska Institutet [Stockholm]
10 Radboud University Medical Center [Nijmegen]
11 UPMC - Université Pierre et Marie Curie - Paris 6
12 Hospital Virgen de la Salud
13 HCL - Hospices Civils de Lyon
14 General Hospital of Thessaloniki George Papanikolaou
15 Evangelismos Athens General Hospital
16 UOC - University of Crete [Heraklion]
17 Department of Informatics [Ionian University]
18 IRCCS San Raffaele Scientific Institute [Milan, Italie]
19 IGH - Institut de génétique humaine
20 CAM - University of Cambridge [UK]
21 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
22 ITI - Informatics & Telematics Institute
23 CERTH - Centre for Research and Technology Hellas [Athènes]
Frédéric Charlotte
- Fonction : Auteur
- PersonId : 779521
- ORCID : 0000-0003-2803-6606
Zadie Davi
- Fonction : Auteur
Ana Juan Ferrer
- Fonction : Auteur
- PersonId : 996071
Panayiotis Vlamos
- Fonction : Auteur
- PersonId : 1000689
Maurilio Ponzoni
- Fonction : Auteur
- PersonId : 882038
Véronique Giudicelli
- Fonction : Auteur
- PersonId : 1197166
- IdHAL : veronique-giudicelli
- ORCID : 0000-0002-2258-468X
- IdRef : 224422596
Marie-Paule Lefranc
- Fonction : Auteur
- PersonId : 1253455
- ORCID : 0000-0003-0116-9353
- IdRef : 096991046
Blanca Espinet
- Fonction : Auteur
Miguel Angel Piris
- Fonction : Auteur
Chrysoula C Belessi
- Fonction : Auteur
David Oscier
- Fonction : Auteur
Frederic Davi
- Fonction : Auteur
- PersonId : 1239877
- ORCID : 0000-0002-3764-063X
Résumé
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. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.