Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA.
Bristol-Meyers Squibb, Princeton, NJ, USA.
FEBS Lett. 2020 Oct;594(20):3324-3337. doi: 10.1002/1873-3468.13903. Epub 2020 Aug 29.
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.
哺乳动物的体液免疫依赖于两种在发育和功能上明显不同的 B 细胞亚群——B1 和 B2 细胞。B2 细胞负责对环境抗原的适应性反应，而 B1 细胞调节先天体液免疫中多反应性和低亲和力抗体的产生。B 细胞分化为不同亚群的分子机制研究较少。在这项研究中，我们鉴定出赖氨酸甲基转移酶 NSD2（MMSET/WHSC1）是 B1 细胞发育的关键调节因子。与 NSD2 对 B2 细胞的影响较小相反，在原代 B 细胞中缺失 NSD2 的催化结构域会损害 B1 谱系的产生。因此，组蛋白 H3 K36 二甲基转移酶 NSD2 是小鼠 B 细胞谱系中首个具有独特功能的表观遗传调节剂。
