CXCR4 expression functionally discriminates centroblasts versus centrocytes within human germinal center B cells. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue American Journal of Immunology Année : 2009

CXCR4 expression functionally discriminates centroblasts versus centrocytes within human germinal center B cells.

Résumé

The human germinal center is a highly dynamic structure where B cells conduct their terminal differentiation and traffic following chemokine gradients. The rapidly dividing centroblasts and the nondividing centrocytes represent the two major B cell subsets present in germinal center and also the most common normal counterparts for a majority of lymphomas. CD77 expression was previously associated to proliferating centroblasts undergoing somatic hypermutation, but data from transcriptional studies demonstrate that CD77 is not a reliable marker to discriminate human centroblasts from centrocytes. Herein we were able for the first time to separate these two subpopulations based on the expression of the chemokine receptor CXCR4 allowing their characterization. Phenotypic and functional features were especially explored, giving an accurate definition of CXCR4(+) centroblasts compared with CXCR4(-) centrocytes. We show that CXCR4(+) and CXCR4(-) germinal center B cells present a clear dichotomy in terms of proliferation, transcription factor expression, Ig production, and somatic hypermutation regulation. Microarray analysis identified an extensive gene list segregating these B cells, including highly relevant genes according to previous knowledge. By gene set enrichment analysis we demonstrated that the centroblastic gene expression signature was significantly enriched in Burkitt's lymphomas. Collectively, our findings show that CXCR4 expression can properly separate human centroblasts from centrocytes and offer now the possibility to have purified normal counterparts of mature B cell-derived malignancies.

Domaines

Cancer

Dates et versions

inserm-00869387 , version 1 (03-10-2013)

Identifiants

Citer

Gersende Caron, Simon Le Gallou, Thierry Lamy, Karin Tarte, Thierry Fest. CXCR4 expression functionally discriminates centroblasts versus centrocytes within human germinal center B cells.. American Journal of Immunology, 2009, 182 (12), pp.7595-602. ⟨10.4049/jimmunol.0804272⟩. ⟨inserm-00869387⟩
106 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More