title: Human t(14;18)positive germinal center B cells: a new step in follicular lymphoma pathogenesis?
abstract: Follicular lymphoma (FL) is a B-cell neoplasm resulting from the transformation of germinal center (GC) B cells. Although t(14;18) and ectopic B-cell lymphoma 2 (BCL2) expression constitute the genetic hallmark of FL, t(14;18)(pos) B cells bearing genotypic and phenotypic features of FL cells can be found in the blood of most healthy individuals. Nevertheless, the localization of these FL-like cells (FLLCs) in nonmalignant GC-rich tissues and the functional consequences of BCL2 overexpression have not been evaluated thus far. Among 85 reactive lymph node (RLN) samples, 14% were found to contain high levels of t(14;18) by quantitative polymerase chain reaction. In t(14;18)(hi) RLNs, CD20(pos)BCL2(pos)CD10(pos) FLLCs consistently accumulated within the GC, essentially as nonproliferative CXCR4(neg) centrocytes. Moreover, they displayed a reduced response to proliferative stimuli in vitro. Altogether, our findings provide new insights into in situ FLLC functional properties and suggest that these cells have not acquired the ultimate genetic events leading to FL transformation.
authors.affiliation: Centre d'Immunologie Marseille-Luminy, Université Aix-Marseille, Marseille, France; INSERM, Unité Mixte de Recherche U1104, Marseille, France; Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7280, Marseille, France;
authors.forename: Julie
authors.initials: J
authors.lastname: Tellier
authors.affiliation: INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France; Centre Hospitalier Universitaire de Rennes, Service Immunologie, Thérapie Cellulaire et Hématopoïèse, Rennes, France;
authors.forename: Cedric
authors.initials: C
authors.lastname: Menard
authors.affiliation: Centre d'Immunologie Marseille-Luminy, Université Aix-Marseille, Marseille, France; INSERM, Unité Mixte de Recherche U1104, Marseille, France; Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7280, Marseille, France;
authors.forename: Sandrine
authors.initials: S
authors.lastname: Roulland
authors.affiliation: INSERM U955, Créteil, France; Université Paris-Est, Créteil, France; and.
authors.forename: Nadine
authors.initials: N
authors.lastname: Martin
authors.affiliation: INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Céline
authors.initials: C
authors.lastname: Monvoisin
authors.affiliation: Centre d'Immunologie Marseille-Luminy, Université Aix-Marseille, Marseille, France; INSERM, Unité Mixte de Recherche U1104, Marseille, France; Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7280, Marseille, France;
authors.forename: Lionel
authors.initials: L
authors.lastname: Chasson
authors.affiliation: Centre d'Immunologie Marseille-Luminy, Université Aix-Marseille, Marseille, France; INSERM, Unité Mixte de Recherche U1104, Marseille, France; Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7280, Marseille, France;
authors.forename: Bertrand
authors.initials: B
authors.lastname: Nadel
authors.affiliation: INSERM U955, Créteil, France; Université Paris-Est, Créteil, France; and Hôpital Henri Mondor, Département de Pathologie, Assistance Publique - Hôpitaux de Paris, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.affiliation: Centre d'Immunologie Marseille-Luminy, Université Aix-Marseille, Marseille, France; INSERM, Unité Mixte de Recherche U1104, Marseille, France; Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7280, Marseille, France;
authors.forename: Claudine
authors.initials: C
authors.lastname: Schiff
authors.affiliation: INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France; Centre Hospitalier Universitaire de Rennes, Service Immunologie, Thérapie Cellulaire et Hématopoïèse, Rennes, France;
authors.forename: Karin
authors.identifier: http://orcid.org/0000-0002-6809-917X
authors.initials: K
authors.lastname: Tarte
mesh_terms: D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D005260:Female; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D018951:Antigens, CD20; D019253:Proto-Oncogene Proteins c-bcl-2; D015260:Neprilysin