Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells

Archive ouverte

Caron, Gersende | Hussein, Mourad | Kulis, Marta | Delaloy, Céline | Chatonnet, Fabrice | Pignarre, Amandine | Avner, Stéphane | Lemarié, Maud | Mahé, Elise A. | Verdaguer-Dot, Nuria | Queiros, Ana C. | Tarte, Karin | Martin-Subero, José I. | Salbert, Gilles | Fest, Thierry

Edité par CCSD ; Elsevier Inc -

International audience. Molecular mechanisms underlying terminal differen­tiation of B cells into plasma cells are major determi­nants of adaptive immunity but remain only partially understood. Here we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B cells and differenti­ation into plasmablasts. Cell proliferation of acti­vated B cells was linked to a slight decrease in DNA methylation levels, but followed by a committal step in which an S phase-synchronized differentia­tion switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxyme­thylcytosine at enhancers and genes related to plasma cell identity. Downregulation of both TGF­β1/SMAD3 signaling and p53 pathway supported this final step, allowing the emergence of a CD23­-negative subpopulation in transition from B cells to plasma cells. Remarkably, hydroxymethylation of PRDM1, a gene essential for plasma cell fate, was coupled to progression in S phase, revealing an intri­cate connection among cell cycle, DNA (hydroxy) methylation, and cell fate determination.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion