Zhu Gaizhi, Wang Xiaoqian, Xiao He, Liu Xiaoling, Fang Ying, Zhai Bing, Xu Ruonan, Han Gencheng, Chen Guojiang, Hou Chunmei, Shen Beifen, Li Yan, Ma Ning, Wu Haitao, Liu Guangchao, Wang Renxi
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; Joint National Laboratory for Antibody Drug Engineering, Henan University, Kaifeng, Henan 475004, China.
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
Mol Immunol. 2017 Nov;91:17-23. doi: 10.1016/j.molimm.2017.08.021. Epub 2017 Aug 31.
Notch1 signaling regulates B and T lymphocyte development and also in vitro promotes antibody secretion upon B cell activation. However, it is still unclear about the role of Notch1 in antibody production upon in vitro and in vivo mixture lymphocytes activation. We first showed that Notch1 expressed in LPS-activated CD19 B cells and CD19 mediated Notch1 knock-down in LPS-activated B cells. Furthermore, we demonstrated that Notch1 knock-down in B cells reduced antibody production in LPS-stimulated B cells but did not affect antibody production in LPS-stimulated splenocytes and in experimental allergic encephalomyelitis (EAE) mice. Importantly, Notch1 ligands Dll1 and Jag1 expressed in B cells and pre-coated Notch1 protein promotes Notch1-knocked down B cells to produce antibody in LPS-stimulated B cells suggesting that Notch1 in other cells may promote antibody production by binding its ligands Dll1 and Jag1 in B cells. Together, our results suggest that both Notch1 and its ligands in B cells play an important role in antibody production.
Notch1信号通路调节B淋巴细胞和T淋巴细胞的发育，并且在体外B细胞活化时促进抗体分泌。然而，Notch1在体外和体内混合淋巴细胞活化时在抗体产生中的作用仍不清楚。我们首先发现Notch1在LPS激活的CD19 B细胞中表达，且CD19介导LPS激活的B细胞中Notch1的敲低。此外，我们证明B细胞中Notch1的敲低降低了LPS刺激的B细胞中的抗体产生，但不影响LPS刺激的脾细胞和实验性自身免疫性脑脊髓炎（EAE）小鼠中的抗体产生。重要的是，B细胞中表达的Notch1配体Dll1和Jag1以及预包被的Notch1蛋白促进了LPS刺激的B细胞中Notch1敲低的B细胞产生抗体，这表明其他细胞中的Notch1可能通过与B细胞中的配体Dll1和Jag1结合来促进抗体产生。总之，我们的结果表明B细胞中的Notch1及其配体在抗体产生中起重要作用。
