Chen Xiangjun, Pan Weiling, Sui Yinqiang, Li Hua, Shi Xiaoshan, Guo Xingdong, Qi Hai, Xu Chenqi, Liu Wanli
MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Tsinghua University, Beijing 100084, China.
State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Nat Commun. 2015 Oct 6;6:8552. doi: 10.1038/ncomms9552.
B cells that express the isotype-switched IgG-B cell receptor (IgG-BCR) are one of the driving forces for antibody memory. To allow for a rapid memory IgG antibody response, IgG-BCR evolved into a highly effective signalling machine. Here, we report that the positively charged cytoplasmic domain of mIgG (mIgG-tail) specifically interacts with negatively charged acidic phospholipids. The key immunoglobulin tail tyrosine (ITT) in mIgG-tail is thus sequestered in the membrane hydrophobic core in quiescent B cells. Pre-disruption of such interaction leads to excessive recruitment of BCRs and inflated BCR signalling upon antigen stimulation, resulting in hyperproliferation of primary B cells. Physiologically, membrane-sequestered mIgG-tail can be released by antigen engagement or Ca(2+) mobilization in the initiation of B cell activation. Our studies suggest a novel regulatory mechanism for how dynamic association of mIgG-tail with acidic phospholipids governs the enhanced activation of IgG-BCR.
表达同种型转换的IgG-B细胞受体（IgG-BCR）的B细胞是抗体记忆的驱动力量之一。为了实现快速的记忆性IgG抗体反应，IgG-BCR进化成为一种高效的信号传导机器。在此，我们报告mIgG的带正电荷的胞质结构域（mIgG尾部）特异性地与带负电荷的酸性磷脂相互作用。因此，mIgG尾部中的关键免疫球蛋白尾部酪氨酸（ITT）在静止B细胞中被隔离在膜疏水核心中。这种相互作用的预先破坏会导致抗原刺激时BCR过度募集和BCR信号增强，从而导致原代B细胞过度增殖。在生理上，膜隔离的mIgG尾部可以在B细胞活化起始时通过抗原结合或Ca(2+)动员而释放。我们的研究提出了一种新的调节机制，即mIgG尾部与酸性磷脂的动态结合如何控制IgG-BCR的增强活化。
