%0 Journal Article %T PI(4,5)P2 determines the threshold of mechanical force¨Cinduced B cell activation %A Chen %A Chenguang %A Chenguang Xu %A Fei %A Fei Wang %A Haodong %A Haodong Chen %A Hengyi %A Hengyi Xie %A Ji %A Ji-Shen %A Ji-Shen Zheng %A Jing %A Jing Wang %A Jizhong %A Jizhong Lou %A Li %A Liu %A Lou %A Qinghua %A Qinghua Ji %A Samina %A Samina Shaheen %A Shaheen %A Tang %A Wan %A Wang %A Wanli Liu %A Wei %A Wei Chen %A Xiangjun %A Xiangjun Chen %A Xie %A Xingyu %A Xingyu Ji %A Xu %A Yang %A Yang Xu %A Zheng %A Zhengpeng %A Zhengpeng Wan %A Zhuo %A Zhuo Tang %A Zongyu %A Zongyu Li %J JCB | The Journal of Cell Biology %D 2018 %R 10.1083/jcb.201711055 %X 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. %U http://jcb.rupress.org/content/217/7/2565