Ion channel TRPV2 is critical in enhancing B cell activation and function

Author:

Li Cuifeng12ORCID,Zhao Meng1ORCID,Liu Xiaohang1ORCID,Li Yuxin1ORCID,Xu Bihua34ORCID,Zhou Lina56ORCID,Sun Xiaolin78ORCID,Sun Wenbo1ORCID,Kang Na1ORCID,Ji Zhenglin1ORCID,Li Tong1ORCID,An Haoran9ORCID,Wang Fei10ORCID,Wu Chuan11ORCID,Ye Jing-Ying1ORCID,Zhang Jing-Ren29ORCID,Wang Qingwen34ORCID,Zhao Xiaodong612ORCID,Li Zhanguo278ORCID,Liu Wanli12ORCID

Affiliation:

1. Tsinghua University 1 State Key Laboratory of Membrane Biology, School of Life Sciences, Institute for Immunology, China Ministry of Education Key Laboratory of Protein Sciences, Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing Tsinghua Changgung Hospital, , Beijing, China

2. Tsinghua-Peking Center for Life Sciences 2 , Beijing, China

3. Peking University Shenzhen Hospital 3 Department of Rheumatism and Immunology, , Shenzhen, China

4. Shenzhen Key Laboratory of Inflammatory and Immunology Diseases 4 , Shenzhen, China

5. Children’s Hospital of Chongqing Medical University 5 Department of Pediatric Research Institute, , Chongqing, China

6. Children’s Hospital of Chongqing Medical University 6 Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, , Chongqing, PR China

7. Peking University People’s Hospital 7 Department of Rheumatology and Immunology, , Beijing, China

8. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) 8 , Beijing, China

9. Tsinghua University 9 Center for Infectious Disease Research, School of Medicine, , Beijing, China

10. Chengdu Institute of Biology, Chinese Academy of Sciences 10 , Chengdu, China

11. National Cancer Institute, National Institutes of Health 11 Experimental Immunology Branch, , Bethesda, MD, USA

12. Children’s Hospital of Chongqing Medical University 12 Department of Rheumatology and Immunology, , Chongqing, China

Abstract

The function of transient receptor potential vanilloid (TRPV) cation channels governing B cell activation remains to be explored. We present evidence that TRPV2 is highly expressed in B cells and plays a crucial role in the formation of the B cell immunological synapse and B cell activation. Physiologically, TRPV2 expression level is positively correlated to influenza-specific antibody production and is low in newborns and seniors. Pathologically, a positive correlation is established between TRPV2 expression and the clinical manifestations of systemic lupus erythematosus (SLE) in adult and child SLE patients. Correspondingly, mice with deficient TRPV2 in B cells display impaired antibody responses following immunization. Mechanistically, the pore and N-terminal domains of TRPV2 are crucial for gating cation permeation and executing mechanosensation in B cells upon antigen stimulation. These processes synergistically contribute to membrane potential depolarization and cytoskeleton remodeling within the B cell immunological synapse, fostering efficient B cell activation. Thus, TRPV2 is critical in augmenting B cell activation and function.

Funder

Ministry of Science and Technology of China

National Natural Science Foundation of China

Beijing Natural Science Foundation

Shenzhen Medical Research Fund

Key Project of Basic Research of Shenzhen Science and Technology Innovation Commission

Shenzhen Municipal Health Commission

National Multiple Sclerosis Society

Tsinghua University Spring Breeze Fund

Center for Life Sciences

Institute for Immunology at Tsinghua University

Vanke School of Public Health at Tsinghua University

Publisher

Rockefeller University Press

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