B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation.
Nat Commun
; 9(1): 1900, 2018 05 15.
Article
em En
| MEDLINE
| ID: mdl-29765016
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
/
Linfócitos B
/
Metilação de DNA
/
DNA (Citosina-5-)-Metiltransferases
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article