The histone methyltransferase DOT1L is essential for humoral immune responses
- Author(s)
- Kealy, L; Di Pietro, A; Hailes, L; Scheer, S; Dalit, L; Groom, JR; Zaph, C; Good-Jacobson, KL;
- 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
- Research Division(s)
- Immunology
- PubMed ID
- 33326791
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2020.108504
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2020.108504- Terms of Use/Rights Notice
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Creation Date: 2021-02-01 12:08:34
Last Modified: 2021-03-02 02:31:01