A PIP2-derived amplification loop fuels the sustained initiation of B cell activation

doi:10.1126/sciimmunol.aan0787

	A PIP2-derived amplification loop fuels the sustained initiation of B cell activation
	Xu, Chenguang 1; Xie, Hengyi 1; Guo, Xingdong 2; Gong, Haipeng 3; Liu, Lei 4; Qi, Hai 5; Xu, Chenqi2,6 ; Liu, Wanli 1
	2017-11
发表期刊	SCIENCE IMMUNOLOGY
ISSN	2470-9468
卷号	2 期号:17
发表状态	已发表
DOI	10.1126/sciimmunol.aan0787
摘要	Lymphocytes have evolved sophisticated signaling amplification mechanisms to efficiently activate downstream signaling after detection of rare ligands in their microenvironment. B cell receptor microscopic clusters (BCR microclusters) are assembled on the plasma membrane and recruit signaling molecules for the initiation of lymphocyte signaling after antigen binding. We identified a signaling amplification loop derived from phosphatidylinositol 4,5-biphosphate (PIP2) for the sustained B cell activation. Upon antigen recognition, PIP 2 was depleted by phospholipase C-gamma 2 (PLC, gamma 2) within the BCR microclusters and was regenerated by phosphatidic acid-dependent type I phosphatidylinositol 4-phosphate 5-kinase outside the BCR microclusters. The hydrolysis of PIP2 inside the BCR microclusters induced a positive feedback mechanism for its synthesis outside the BCR microclusters. The falling gradient of PIP2 across the boundary of BCR microclusters was important for the efficient formation of BCR microclusters. Our results identified a PIP2 -derived amplification loop that fuels the sustained initiation of B cell activation.
收录类别	SCI
语种	英语
资助项目	Ministry of Science and Technology of China[2014CB542500-03]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000434328500002
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS关键词	PHOSPHATIDYLINOSITOL 4-PHOSPHATE ; MEDIATED ACTIVATION ; PHOSPHATIDIC-ACID ; PHOSPHOLIPASE-C ; KINASE ; DYNAMICS ; MICROCLUSTERS ; MECHANISMS ; MOLECULES ; 5-KINASE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/23084
专题	生命科学与技术学院_特聘教授组_许琛琦组
通讯作者	Liu, Wanli
作者单位	1.Tsinghua Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Sch Life Sci, Inst Immunol,MOE,Key Lab Prot Sci, Beijing 100084, Peoples R China 2.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci,State Key Lab Mol Biol, Shanghai 200031, Peoples R China 3.Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China 4.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Dept Chem, Key Lab Bioorgan Phosphorus Chem & Chem Biol MOE, Beijing 100084, Peoples R China 5.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Sch Med, Lab Dynam Immunobiol, Beijing 100084, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Xu, Chenguang,Xie, Hengyi,Guo, Xingdong,et al. A PIP2-derived amplification loop fuels the sustained initiation of B cell activation[J]. SCIENCE IMMUNOLOGY,2017,2(17).
APA	Xu, Chenguang.,Xie, Hengyi.,Guo, Xingdong.,Gong, Haipeng.,Liu, Lei.,...&Liu, Wanli.(2017).A PIP2-derived amplification loop fuels the sustained initiation of B cell activation.SCIENCE IMMUNOLOGY,2(17).
MLA	Xu, Chenguang,et al."A PIP2-derived amplification loop fuels the sustained initiation of B cell activation".SCIENCE IMMUNOLOGY 2.17(2017).