Notch activity synergizes with B-cell-receptor and CD40 signaling to enhance B-cell activation
Notch activity synergizes with B-cell-receptor and CD40 signaling to enhance B-cell activation
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DOI：
10.1182/blood-2006-09-046698
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发表时间：
2007-04-15
期刊：
影响因子：
20.3
通讯作者：
Allman, David
中科院分区：
文献类型：
--
作者：
Thomas, Matthew;Calamito, Marco;Allman, David
如何整合不同的环境信号来调节 B 细胞的激活和发育仍然知之甚少。在这里，我们展示了 Notch 活性与 B 细胞受体 (BCR) 和/或 CD40 信号传导协同作用，以增强 B 细胞激活和功能的多个方面。我们发现滤泡 B 细胞与 Notch 配体 Delta-like-1 的共刺激导致 BCR 和 CD40 介导的增殖显着增加，并增强体外和体内 IgG1(+) 细胞的产生。我们进一步发现Notch和BCR的共同接合导致MAPK途径的激活增加，并且MAPK和Notch抑制剂阻止Notch和BCR共同接合介导的B细胞活化事件。这些数据表明 BCR 和 CD40 信号通路与 Notch 通路协同优化 B 细胞激活。
How diverse environmental cues are integrated to regulate B-cell activation and development remains poorly understood. Here we show that Notch activity synergizes with B-cell receptor (BCR) and/or CD40 signaling to enhance several aspects of B-cell activation and function. We find that costimulation of follicular B cells with the Notch ligand Delta-like-1 leads to significant increases in BCR- and CD40-mediated proliferation and enhances production of IgG1(+) cells in vitro and in vivo. We further find that coengagement of Notch and the BCR results in increased activation of the MAPK pathway, and MAPK and Notch inhibitors prevent B-cell activation events mediated by coengagement of Notch and the BCR. These data suggest that the BCR and CD40 signaling pathways collaborate with the Notch pathway to optimize B-cell activation.