DNA methylation trajectories during innate and adaptive immune responses of human B lymphocytes.
B lymphocyte
DNA methylome
adaptive immunity
epigenetics
innate immunity
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
03
08
2022
accepted:
07
02
2023
medline:
16
6
2023
pubmed:
11
2
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
B lymphocytes can engage in either a rapid T cell-independent pathway (TI) or a delayed long-lasting T cell-independent (TD) response through highly ordered transcriptional programs, yet the detailed underlying mechanisms are unclear. Since DNA methylation plays a key role in controlling gene expression and lineage specification, we explored the dynamics of whole-genome cytosine modifications during the ex vivo response of human B cells isolated from normal individuals by negative selection. We found that B cell differentiation following TI and TD signalling is accompanied by extensive remodelling of the epigenome, including global gain and loss of DNA methylation. The epigenetic changes map to different regions of the B cell genome, including non- C-phosphate-G CpG islands, indicating that modifications of distal regulatory elements likely regulate specific gene transcription in B cells. Non-CpG methylation also occurs in differentiating human B cells, suggesting that this DNA modification is involved in transcriptional regulation of B cell genes with promoters exhibiting a low-density methylation, possibly by changing the chromatin shape that could have an impact on gene expression. Most strikingly, compared to TD activation, stimulation of B cells through an innate pathway induced higher levels of DNA methylation modifications at CpG, CHG and CGG contexts, supporting the view that DNA methylation modifications are used in distinct trajectories to specify the TI and TD B lymphocyte responses.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
344-357Informations de copyright
© 2023 John Wiley & Sons Ltd.
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