eLife (Jul 2017)
Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase
- Samina Shaheen,
- Zhengpeng Wan,
- Zongyu Li,
- Alicia Chau,
- Xinxin Li,
- Shaosen Zhang,
- Yang Liu,
- Junyang Yi,
- Yingyue Zeng,
- Jing Wang,
- Xiangjun Chen,
- Liling Xu,
- Wei Chen,
- Fei Wang,
- Yun Lu,
- Wenjie Zheng,
- Yan Shi,
- Xiaolin Sun,
- Zhanguo Li,
- Chunyang Xiong,
- Wanli Liu
Affiliations
- Samina Shaheen
- ORCiD
- 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, China
- Zhengpeng Wan
- 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, China
- Zongyu Li
- 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, China
- Alicia Chau
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
- Xinxin Li
- ORCiD
- 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, China
- Shaosen Zhang
- 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, China
- Yang Liu
- 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, China
- Junyang Yi
- 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, China
- Yingyue Zeng
- 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, China
- Jing Wang
- 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, China
- Xiangjun Chen
- 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, China
- Liling Xu
- 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, China
- Wei Chen
- School of Medicine, Zhejiang University, Hangzhou, China
- Fei Wang
- Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China
- Yun Lu
- State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, China
- Wenjie Zheng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Yan Shi
- ORCiD
- Center for Life Sciences, Department of Basic Medical Sciences, Institute of Immunology, Tsinghua University, Beijing, China
- Xiaolin Sun
- Department of Rheumatology and Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, China
- Zhanguo Li
- Department of Rheumatology and Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, China
- Chunyang Xiong
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; College of Engineering, Peking University, Beijing, China
- Wanli Liu
- ORCiD
- 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, China
- DOI
- https://doi.org/10.7554/eLife.23060
- Journal volume & issue
-
Vol. 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 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 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 PKCβ-mediated FAK activation dependent manner.
Keywords
