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.

中文翻译：

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组蛋白甲基转移酶 NSD2/MMSET 的催化域是小鼠 B1 细胞生成所必需的

哺乳动物的体液免疫依赖于两种发育和功能不同的 B 细胞亚群——B1 和 B2 细胞的功能。虽然 B2 细胞负责对环境抗原的适应性反应，但 B1 细胞调节多反应性和低亲和力抗体的产生，用于先天体液免疫。B 细胞分化为不同亚群的分子机制尚未得到充分研究。在这项研究中，我们将赖氨酸甲基转移酶 NSD2 (MMSET/WHSC1) 鉴定为 B1 细胞发育的关键调节因子。与它对 B2 细胞的轻微影响相反，原代 B 细胞中 NSD2 催化结构域的缺失会损害 B1 谱系的产生。因此，组蛋白 H3 K36 二甲基酶 NSD2 是小鼠 B 细胞谱系的一流表观遗传调节剂。