Plasmablasts derive from CD23-negative activated B cells after the extinction of IL-4/STAT6 signaling and IRF4 induction - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Blood Année : 2021

Plasmablasts derive from CD23-negative activated B cells after the extinction of IL-4/STAT6 signaling and IRF4 induction

Résumé

The terminal differentiation of B cells into antibody-secreting cells (ASCs) is a critical component of adaptive immune responses. However, it is a very sensitive process, and dysfunctions lead to a variety of lymphoproliferative neoplasias including germinal center-derived lymphomas. To better characterize the late genomic events that drive the ASC differentiation of human primary naive B cells, we used our in vitro differentiation system and a combination of RNA sequencing and Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC sequencing). We discovered 2 mechanisms that drive human terminal B-cell differentiation. First, after an initial response to interleukin-4 (IL-4), cells that were committed to an ASC fate downregulated the CD23 marker and IL-4 signaling, whereas cells that maintained IL-4 signaling did not differentiate. Second, human CD23- cells also increased IRF4 protein to levels required for ASC differentiation, but they did that independently of the ubiquitin-mediated degradation process previously described in mice. Finally, we showed that CD23- cells carried the imprint of their previous activated B-cell status, were precursors of plasmablasts, and had a phenotype similar to that of in vivo preplasmablasts. Altogether, our results provide an unprecedented genomic characterization of the fate decision between activated B cells and plasmablasts, which provides new insights into the pathological mechanisms that drive lymphoma biology.

Dates et versions

hal-03016119 , version 1 (20-11-2020)

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Amandine Pignarre, Fabrice Chatonnet, Gersende Caron, Marion Haas, Fabienne Desmots-Loyer, et al.. Plasmablasts derive from CD23-negative activated B cells after the extinction of IL-4/STAT6 signaling and IRF4 induction. Blood, 2021, 137 (9), pp.1166-1180. ⟨10.1182/blood.2020005083⟩. ⟨hal-03016119⟩
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