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

Abstract : 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.
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Submitted on : Friday, October 23, 2015 - 9:34:31 AM
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Gersende Caron, Mourad Hussein, Marta Kulis, Céline Delaloy, Fabrice Chatonnet, et al.. Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells. Cell Reports, Elsevier Inc, 2015, 13 (5), pp.1059-1071. ⟨10.1016/j.celrep.2015.09.051⟩. ⟨hal-01219671⟩

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