期刊
FEBS LETTERS
卷 594, 期 20, 页码 3324-3337出版社
WILEY
DOI: 10.1002/1873-3468.13903
关键词
B1 cells; histone methylation; MMSET; NSD2
资金
- NIH [AI118891, CA196539]
- Leukemia and Lymphoma Robert Arceci Scholar Award
- International Myeloma Foundation
- Wendy Will Case Cancer Fund
- Open Philanthropy Project/Good Ventures Fund
- GlaxoSmithKline
- NATIONAL CANCER INSTITUTE [P01CA196539] Funding Source: NIH RePORTER
Humoral immunity in mammals relies on the function of two developmentally and functionally distinct B-cell subsets-B1 and B2 cells. While B2 cells are responsible for the adaptive response to environmental antigens, B1 cells regulate the production of polyreactive and low-affinity antibodies for innate humoral immunity. The molecular mechanism of B-cell specification into different subsets is understudied. In this study, we identified lysine methyltransferase NSD2 (MMSET/WHSC1) as a critical regulator of B1 cell development. In contrast to its minor impact on B2 cells, deletion of the catalytic domain of NSD2 in primary B cells impairs the generation of B1 lineage. Thus, NSD2, a histone H3 K36 dimethylase, is the first-in-class epigenetic regulator of a B-cell lineage in mice.
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