The class-specific BCR tonic signal modulates lymphomagenesis in a c-myc deregulation transgenic model. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Oncotarget Année : 2014

The class-specific BCR tonic signal modulates lymphomagenesis in a c-myc deregulation transgenic model.

Résumé

Deregulation of c-myc by translocation onto immunoglobulin (Ig) loci can promote B cell malignant proliferations with phenotypes as diverse as acute lymphoid leukemia, Burkitt lymphoma, diffuse large B cell lymphoma, myeloma... The B cell receptor (BCR) normally providing tonic signals for cell survival and mitogenic responses to antigens, can also contribute to lymphomagenesis upon sustained ligand binding or activating mutations. BCR signaling varies among cell compartments and BCR classes. For unknown reasons, some malignancies associate with expression of either IgM or class-switched Ig. We explored whether an IgA BCR, with strong tonic signaling, would affect lymphomagenesis in c-myc IgH 3'RR transgenic mice prone to lymphoproliferations. Breeding c-myc transgenics in a background where IgM expression was replaced with IgA delayed lymphomagenesis. By comparison to single c-myc transgenics, lymphomas from double mutant animals were more differentiated and less aggressive, with an altered transcriptional program. Larger tumor cells more often expressed CD43 and CD138, which culminated in a plasma cell phenotype in 10% of cases. BCR class-specific signals thus appear to modulate lymphomagenesis and may partly explain the observed association of specific Ig classes with human B cell malignancies of differential phenotype, progression and prognosis.

Mots clés

Fichier principal
Vignette du fichier
class-specific_BCR_-version_of_record_-_licence_CC_BY.pdf (1.05 Mo) Télécharger le fichier
class-specific_BCR_-supplementary_data.pdf (1.69 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Format : Autre

Dates et versions

hal-01067143 , version 1 (23-09-2014)

Identifiants

Citer

Rada Amin, Abdelghafour Marfak, Céline Pangault, Christelle Oblet, Aurélie Chanut, et al.. The class-specific BCR tonic signal modulates lymphomagenesis in a c-myc deregulation transgenic model.. Oncotarget, 2014, 5 (19), pp.8995-9006. ⟨10.18632/oncotarget.2297⟩. ⟨hal-01067143⟩
259 Consultations
209 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More