Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ 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 PKCβ can bypass the Btk...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-07-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/23060 |
| _version_ | 1818019821986512896 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Samina Shaheen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:56:40Z |
| format | Article |
| id | doaj.art-53442122ceb94add81f255cfd8082d1e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:56:40Z |
| publishDate | 2017-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-53442122ceb94add81f255cfd8082d1e2022-12-22T02:05:01ZengeLife Sciences Publications LtdeLife2050-084X2017-07-01610.7554/eLife.23060Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinaseSamina Shaheen0https://orcid.org/0000-0003-2890-6827Zhengpeng Wan1Zongyu Li2Alicia Chau3Xinxin Li4https://orcid.org/0000-0003-0055-1999Shaosen Zhang5Yang Liu6Junyang Yi7Yingyue Zeng8Jing Wang9Xiangjun Chen10Liling Xu11Wei Chen12Fei Wang13Yun Lu14Wenjie Zheng15Yan Shi16https://orcid.org/0000-0002-6715-7681Xiaolin Sun17Zhanguo Li18Chunyang Xiong19Wanli Liu20https://orcid.org/0000-0003-0395-2800MOE 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, ChinaMOE 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, ChinaMOE 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, ChinaAcademy for Advanced Interdisciplinary Studies, Peking University, Beijing, ChinaMOE 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, ChinaMOE 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, ChinaMOE 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, ChinaMOE 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, ChinaMOE 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, ChinaMOE 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, ChinaMOE 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, ChinaMOE 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, ChinaSchool of Medicine, Zhejiang University, Hangzhou, ChinaChengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, ChinaState Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaCenter for Life Sciences, Department of Basic Medical Sciences, Institute of Immunology, Tsinghua University, Beijing, ChinaDepartment of Rheumatology and Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, ChinaDepartment of Rheumatology and Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, ChinaAcademy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; College of Engineering, Peking University, Beijing, ChinaMOE 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, ChinaThe 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.https://elifesciences.org/articles/23060MechanosensingB cellSubstrate StiffnessPKCβFocal adhesion kinase |
| spellingShingle | 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 Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase eLife Mechanosensing B cell Substrate Stiffness PKCβ Focal adhesion kinase |
| title | Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase |
| title_full | Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase |
| title_fullStr | Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase |
| title_full_unstemmed | Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase |
| title_short | Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase |
| title_sort | substrate stiffness governs the initiation of b cell activation by the concerted signaling of pkcβ and focal adhesion kinase |
| topic | Mechanosensing B cell Substrate Stiffness PKCβ Focal adhesion kinase |
| url | https://elifesciences.org/articles/23060 |
| work_keys_str_mv | AT saminashaheen substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT zhengpengwan substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT zongyuli substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT aliciachau substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT xinxinli substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT shaosenzhang substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT yangliu substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT junyangyi substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT yingyuezeng substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT jingwang substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT xiangjunchen substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT lilingxu substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT weichen substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT feiwang substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT yunlu substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT wenjiezheng substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT yanshi substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT xiaolinsun substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT zhanguoli substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT chunyangxiong substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase AT wanliliu substratestiffnessgovernstheinitiationofbcellactivationbytheconcertedsignalingofpkcbandfocaladhesionkinase |