B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation

Nature Communications
Benjamin G BarwickJeremy M Boss

Abstract

B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization. Gene expression is mostly unaltered in naive and germinal center B cells, but dysregulated in Dnmt3-deficient plasma cells. Differences in gene expression are proximal to Dnmt3-dependent DNA methylation and chromatin changes, both of which coincide with E2A and PU.1-IRF composite-binding motifs. Thus, de novo DNA methylation limits B cell activation, represses the plasma cell chromatin state, and regulates plasma cell differentiation.

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Citations

Sep 21, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert R HainesJeremy M Boss
Mar 16, 2019·Immunological Reviews·Yan Zhang, Kim L Good-Jacobson
Jul 3, 2019·Nature Immunology·Christopher D ScharerJeremy M Boss
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Sep 8, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert R HainesJeremy M Boss
Aug 12, 2020·Nature Communications·Christopher D ScharerJeremy M Boss
Jun 25, 2019·Frontiers in Immunology·Benjamin G BarwickLawrence H Boise
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Datasets Mentioned

BETA
GSE51336
43
GSE89471

Methods Mentioned

BETA
FACS
RNA-seq
footprinting
FCS
ELISA
immunoprecipitation

Software Mentioned

FastQC
Bismark
HOMER
Zen
Rsamtools
EdgeR
FACSDiva
R scripts
Bioconductor GOStats package
flowCore

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