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Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase
- Source :
- eLife, Vol 6 (2017)
- Publication Year :
- 2017
- Publisher :
- eLife Sciences Publications Ltd, 2017.
-
Abstract
- The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKCβ can bypass the Btk and PLC-γ2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKCβ-dependent activation of FAK is required, leading to FAK-mediated potentiation of B cell spreading and adhesion responses. FAK inactivation or deficiency impaired B cell discrimination of substrate stiffness. Conversely, adhesion molecules greatly enhanced this capability of B cells. Lastly, B cells derived from rheumatoid arthritis (RA) patients exhibited an altered BCR response to substrate stiffness in comparison with healthy controls. These results provide a molecular explanation of how initiation of B cell activation discriminates substrate stiffness through a PKCβ-mediated FAK activation dependent manner.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.53442122ceb94add81f255cfd8082d1e
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.23060