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

Benjamin G. Barwick, Christopher D. Scharer, Ryan J. Martinez, Madeline J. Price, Alexander N. Wein, Robert R. Haines, Alexander P. R. Bally, Jacob E. Kohlmeier and Jeremy M. Boss ()
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Benjamin G. Barwick: Emory University School of Medicine
Christopher D. Scharer: Emory University School of Medicine
Ryan J. Martinez: Emory University School of Medicine
Madeline J. Price: Emory University School of Medicine
Alexander N. Wein: Emory University School of Medicine
Robert R. Haines: Emory University School of Medicine
Alexander P. R. Bally: Emory University School of Medicine
Jacob E. Kohlmeier: Emory University School of Medicine
Jeremy M. Boss: Emory University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04234-4

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