Both Notch1 and its ligands in B cells promote antibody production

Both Notch1 and its ligands in B cells promote antibody production
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DOI:
10.1016/j.molimm.2017.08.021
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发表时间:
2017-11
影响因子:
3.6
通讯作者:
G. Zhu;Xiaoqian Wang;He Xiao;Xiaoling Liu;Ying Fang;B. Zhai;R. Xu;G. Han;Guojiang Chen
G. Zhu;Xiaoqian Wang;He Xiao;Xiaoling Liu;Ying Fang;B. Zhai;R. Xu;G. Han;Guojiang Chen
中科院分区:
医学3区
文献类型:
--
作者:
G. Zhu;Xiaoqian Wang;He Xiao;Xiaoling Liu;Ying Fang;B. Zhai;R. Xu;G. Han;Guojiang Chen

文献摘要

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NOTCH1信号调节B和T淋巴细胞的发育,试管蛋白还促进B细胞活化时抗体的分泌。然而,Notch1在抗体生成、体内抗体生成和活体混合淋巴细胞活化中的作用尚不清楚。我们首次发现Notch1在脂多糖激活的CD19hiB细胞中表达,CD19受体介导的Notch1在脂多糖激活的B细胞中表达下调。此外,我们还证明,在B细胞中,Notch1基因敲除降低了内毒素刺激的B细胞中的抗体产生,但不影响内毒素刺激的脾细胞和实验性变态反应性脑脊髓炎(EAE)小鼠的抗体产生。重要的是,Notch1配体Dll1和Jag1在B细胞中表达,预包被的Notch1蛋白促进Notch1被击倒的B细胞在脂多糖刺激的B细胞中产生抗体,这表明其他细胞中的Notch1可能通过与B细胞中的其配体Dll1和Jag1结合来促进抗体的产生。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发挥着重要作用。
Notch1 signaling regulates B and T lymphocyte development and alsoin vitropromotes antibody secretion upon B cell activation. However, it is still unclear about the role of Notch1 in antibody production uponin vitroandin vivomixture lymphocytes activation. We first showed that Notch1 expressed in LPS-activated CD19hiB cells and CD19cremediated 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.