| First Author | Shaheen S | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28755662 | Mgi Jnum | J:259881 |
| Mgi Id | MGI:6141163 | Doi | 10.7554/eLife.23060 |
| Citation | Shaheen S, et al. (2017) Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCbeta and focal adhesion kinase. Elife 6:e23060 |
| abstractText | 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 PKCbeta can bypass the Btk and PLC-gamma2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKCbeta-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 PKCbeta-mediated FAK activation dependent manner. |
