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

• DOI: 10.1083/jcb.201711055
• Publication Date: 2018-04-23T13:15:14Z
• Authors: Zhengpeng Wan; Chenguang Xu; Xiangjun Chen; Hengyi Xie; Zongyu Li; Jing Wang; Xingyu Ji; Haodong Chen; Qinghua Ji; Samina Shaheen; Yang Xu; Fei Wang; Zhuo Tang; Ji-Shen Zheng; Wei Chen; Jizhong Lou; Wanli Liu
• Keywords: breakpoint cluster region; Immunoglobulin heavy chain

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