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

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 respon

SUBMITTER: Shaheen S 

PROVIDER: S-EPMC5536945 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature