TY - JOUR
T1 - Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations
AU - Xochelli, Aliki
AU - Bikos, Vasilis
AU - Polychronidou, Eleftheria
AU - Galigalidou, Chrysi
AU - Agathangelidis, Andreas
AU - Charlotte, Frédéric
AU - Moschonas, Panagiotis
AU - Davis, Zadie
AU - Colombo, Monica
AU - Roumelioti, Maria
AU - Sutton, Lesley-Ann
AU - Groenen, Patricia
AU - van den Brand, Michiel
AU - Boudjoghra, Myriam
AU - Algara, Patricia
AU - Traverse-Glehen, Alexandra
AU - Ferrer, Ana
AU - Stalika, Evangelia
AU - Karypidou, Maria
AU - Kanellis, George
AU - Kalpadakis, Christina
AU - Mollejo, Manuella
AU - Pangalis, Gerasimos
AU - Vlamos, Panayiotis
AU - Amini, Rose-Marie
AU - Pospisilova, Sarka
AU - Gonzalez, David
AU - Ponzoni, Maurilio
AU - Anagnostopoulos, Achilles
AU - Giudicelli, Véronique
AU - Lefranc, Marie-Paule
AU - Espinet, Blanca
AU - Panagiotidis, Panagiotis
AU - Piris, Miguel Angel
AU - Du, Ming-Qing
AU - Rosenquist, Richard
AU - Papadaki, Theodora
AU - Belessi, Chrysoula
AU - Ferrarini, Manlio
AU - Oscier, David
AU - Tzovaras, Dimitrios
AU - Ghia, Paolo
AU - Davi, Frederic
AU - Hadzidimitriou, Anastasia
AU - Stamatopoulos, Kostas
N1 - This article is protected by copyright. All rights reserved.
PY - 2018/11/28
Y1 - 2018/11/28
N2 - The B cell receptor immunoglobulin (BcR 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 World Health Organization 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 spleen 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.
AB - The B cell receptor immunoglobulin (BcR 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 World Health Organization 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 spleen 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.
U2 - 10.1002/path.5209
DO - 10.1002/path.5209
M3 - Article
C2 - 30484876
SN - 0022-3417
JO - Journal of Pathology
JF - Journal of Pathology
ER -