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| A PIP2-derived amplification loop fuels the sustained initiation of B cell activation | |
| 2017-11 | |
| Source Publication | SCIENCE IMMUNOLOGY
 |
| ISSN | 2470-9468 |
| Volume | 2Issue:17 |
| Status | 已发表 |
| DOI | 10.1126/sciimmunol.aan0787 |
| Abstract | 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. |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | Ministry of Science and Technology of China[2014CB542500-03] |
| WOS Research Area | Immunology |
| WOS Subject | Immunology |
| WOS ID | WOS:000434328500002 |
| Publisher | AMER ASSOC ADVANCEMENT SCIENCE |
| WOS Keyword | PHOSPHATIDYLINOSITOL 4-PHOSPHATE ; MEDIATED ACTIVATION ; PHOSPHATIDIC-ACID ; PHOSPHOLIPASE-C ; KINASE ; DYNAMICS ; MICROCLUSTERS ; MECHANISMS ; MOLECULES ; 5-KINASE |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/23084 |
| Collection | 生命科学与技术学院_特聘教授组_许琛琦组 |
| Corresponding Author | Liu, Wanli |
| Affiliation | 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 |
| Recommended Citation 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). |
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