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Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKC\u03b2 can bypass the Btk and PLC-\u03b32 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKC\u03b2-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\u03b2-mediated FAK activation dependent manner.<\/jats:p>","DOI":"10.7554\/elife.23060","type":"journal-article","created":{"date-parts":[[2017,7,30]],"date-time":"2017-07-30T20:00:16Z","timestamp":1501444816000},"source":"Crossref","is-referenced-by-count":69,"title":["Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKC\u03b2 and focal adhesion kinase"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-6827","authenticated-orcid":true,"given":"Samina","family":"Shaheen","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing, 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