Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKC beta and focal adhesion kinase

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 PKC beta can bypass the Btk and PLC-gamma 2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKC beta-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 PKC beta-mediated FAK activation dependent manner.Ministry of Science and Technology of the People's Republic of China [2014CB542500]; National Science Foundation [81422020, 81621002]SCI(E)ARTICLE