Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China.
Reproductive Medicine Centre, Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, China.
Front Immunol. 2022 Nov 30;13:959021. doi: 10.3389/fimmu.2022.959021. eCollection 2022.
B cells, which consist of two well-defined populations: B1 and B2 cells, which can produce antibodies that are essential for host protection against infections, through virus neutralization, opsonization and antibody-dependent cellular cytotoxicity. Epigenetic modifications, such as DNA methylation and histone modification could regulate immune cell differentiation and functions. In this study, we found a significant reduction of GC response in the B cell specific knockout of H3K36 methyltransferase NSD1 (Mb1-Cre NSD1, NSD1) mice compared with the wildtype control (Mb1-Cre NSD1, NSD1). We also demonstrated reduced production of high-affinity antibody, but increased production of low-affinity antibody in the NSD1 mice. Further analysis revealed that loss of NSD1 promoted the development of B1 cells by increasing the expression of Rap1b and Arid3a. In conclusion, our data suggest that NSD1 plays an important role in regulation the development of B1 and B2 cells, and the process of germinal center formation and high-affinity antibody production.
B 细胞包括两个明确的群体：B1 和 B2 细胞，它们可以通过中和病毒、调理作用和抗体依赖性细胞毒性来产生对抗感染至关重要的抗体。表观遗传修饰，如 DNA 甲基化和组蛋白修饰，可以调节免疫细胞的分化和功能。在这项研究中，我们发现与野生型对照相比（Mb1-Cre NSD1，NSD1），B 细胞特异性敲除 H3K36 甲基转移酶 NSD1（Mb1-Cre NSD1，NSD1）的小鼠中 GC 反应明显减少。我们还证明了 NSD1 小鼠中高亲和力抗体的产生减少，但低亲和力抗体的产生增加。进一步分析表明，NSD1 的缺失通过增加 Rap1b 和 Arid3a 的表达促进了 B1 细胞的发育。总之，我们的数据表明 NSD1 在调节 B1 和 B2 细胞的发育以及生发中心形成和高亲和力抗体产生过程中发挥重要作用。
