| Title | Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKC beta and focal adhesion kinase |
| Authors | Shaheen, Samina Wan, Zhengpeng Li, Zongyu Chau, Alicia Li, Xinxin Zhang, Shaosen Liu, Yang Yi, Junyang Zeng, Yingyue Wang, Jing Chen, Xiangjun Xu, Liling Chen, Wei Wang, Fei Lu, Yun Zheng, Wenjie Shi, Yan Sun, Xiaolin Li, Zhanguo Xiong, Chunyang Liu, Wanli |
| Affiliation | Tsinghua Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Key Lab Prot Sci, Sch Life Sci,Inst Immunol,MOE, Beijing, Peoples R China. Peking Univ, Acad Adv Interdisciplinary Studies, Beijing, Peoples R China. Zhejiang Univ, Sch Med, Hangzhou, Zhejiang, Peoples R China. Chinese Acad Sci, Chengdu Inst Biol, Chengdu, Sichuan, Peoples R China. Tsinghua Univ, Sch Environm, State Key Joint Lab Environm Simulat & Pollut Con, Beijing, Peoples R China. Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing, Peoples R China. Chinese Acad Med Sci, Beijing, Peoples R China. Tsinghua Univ, Inst Immunol, Dept Basic Med Sci, Ctr Life Sci, Beijing, Peoples R China. Peking Univ Peoples Hosp, Dept Rheumatol & Immunol, Clin Immunol Ctr, Beijing, Peoples R China. Peking Univ, Coll Engn, Beijing, Peoples R China. |
| Keywords | HIGH EPITOPE DENSITY RHEUMATOID-ARTHRITIS SYNAPSE FORMATION PROTEIN MOLECULE TYROSINE KINASE OUTSIDE-IN C-EPSILON RECEPTOR ANTIGEN INTEGRIN |
| Issue Date | 2017 |
| Publisher | ELIFE |
| Citation | ELIFE.2017,6. |
| 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 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. |
| URI | http://hdl.handle.net/20.500.11897/471988 |
| ISSN | 2050-084X |
| DOI | 10.7554/eLife.23060 |
| Indexed | SCI(E) |
| Appears in Collections: | 前沿交叉学科研究院 人民医院 工学院 |
