Notch activity synergizes with B-cell–receptor and CD40 signaling to enhance B-cell activation
Open Access
- 19 December 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 109 (8), 3342-3350
- https://doi.org/10.1182/blood-2006-09-046698
Abstract
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.Keywords
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