The histone methyltransferase DOT1L is essential for humoral immune responses
Details
Publication Year 2020-12-15, Volume 33, Issue #11, Page 108504
Journal Title
Cell Reports
Publication Type
Journal Article
Abstract
Histone modifiers are essential for the ability of immune cells to reprogram their gene expression during differentiation. The recruitment of the histone methyltransferase DOT1L (disruptor of telomeric silencing 1-like) induces oncogenic gene expression in a subset of B cell leukemias. Despite its importance, its role in the humoral immune system is unclear. Here, we demonstrate that DOT1L is a critical regulator of B cell biology. B cell development is defective in Dot1l(f/f)Mb1(Cre/+) mice, culminating in a reduction of peripheral mature B cells. Upon immunization or influenza infection of Dot1l(f/f)Cd23(Cre/+) mice, class-switched antibody-secreting cells are significantly attenuated and germinal centers fail to form. Consequently, DOT1L is essential for B cell memory formation. Transcriptome, pathway, and histological analyses identified a role for DOT1L in reprogramming gene expression for appropriate localization of B cells during the initial stage of the response. Together, these results demonstrate an essential role for DOT1L in generating an effective humoral immune response.
Publisher
Cell Press
Keywords
B cells; Dot1l; H3k79; antibody; epigenetics; humoral responses
WEHI Research Division(s)
Immunology
PubMed ID
33326791
Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2020.108504
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-02-01 12:08:34
Last Modified: 2021-03-02 02:31:01
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