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J Cell Biol. 2018 Jul 2;217(7):2565-2582. doi: 10.1083/jcb.201711055. Epub 2018 Apr 23.

PI(4,5)P2 determines the threshold of mechanical force-induced B cell activation.

Author information

1
Ministry of Education 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.
2
Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, China.
3
Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
4
School of Life Sciences, University of Science and Technology of China, Hefei, China.
5
School of Basic Medical Sciences, Zhejiang University, Hangzhou, China.
6
Ministry of Education 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 liuwanli@biomed.tsinghua.edu.cn.
7
Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China.

Abstract

B lymphocytes use B cell receptors (BCRs) to sense the chemical and physical features of antigens. The activation of isotype-switched IgG-BCR by mechanical force exhibits a distinct sensitivity and threshold in comparison with IgM-BCR. However, molecular mechanisms governing these differences remain to be identified. In this study, we report that the low threshold of IgG-BCR activation by mechanical force is highly dependent on tethering of the cytoplasmic tail of the IgG-BCR heavy chain (IgG-tail) to the plasma membrane. Mechanistically, we show that the positively charged residues in the IgG-tail play a crucial role by highly enriching phosphatidylinositol (4,5)-biphosphate (PI(4,5)P2) into the membrane microdomains of IgG-BCRs. Indeed, manipulating the amounts of PI(4,5)P2 within IgG-BCR membrane microdomains significantly altered the threshold and sensitivity of IgG-BCR activation. Our results reveal a lipid-dependent mechanism for determining the threshold of IgG-BCR activation by mechanical force.

PMID:
29685902
PMCID:
PMC6028545
DOI:
10.1083/jcb.201711055
[Indexed for MEDLINE]
Free PMC Article

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