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Title: Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells
Author: Caron, Gersende
Hussein, Mourad
Kulis, Marta
Delaloy, Céline
Chatonnet, Fabrice
Pignarre, Amandine
Avner, Stéphane
Lemarié, Maud
Mahé, Elise A.
Verdaguer Dot, Núria
Queirós, Ana C.
Tarte, Karin
Martín Subero, José I.
Salbert, Gilles
Fest, Thierry
Keywords: Cèl·lules B
B cells
Issue Date: 3-Nov-2015
Publisher: Elsevier
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 TGF-β1/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.
Note: Reproducció del document publicat a:
It is part of: Cell Reports, 2015, vol. 13, num. 5, p. 1059-1071
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ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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