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Acidic phospholipids govern the enhanced activation of IgG-B cell receptor

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...

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Autores principales: Chen, Xiangjun, Pan, Weiling, Sui, Yinqiang, Li, Hua, Shi, Xiaoshan, Guo, Xingdong, Qi, Hai, Xu, Chenqi, Liu, Wanli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600742/
https://www.ncbi.nlm.nih.gov/pubmed/26440273
http://dx.doi.org/10.1038/ncomms9552
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author Chen, Xiangjun
Pan, Weiling
Sui, Yinqiang
Li, Hua
Shi, Xiaoshan
Guo, Xingdong
Qi, Hai
Xu, Chenqi
Liu, Wanli
author_facet Chen, Xiangjun
Pan, Weiling
Sui, Yinqiang
Li, Hua
Shi, Xiaoshan
Guo, Xingdong
Qi, Hai
Xu, Chenqi
Liu, Wanli
author_sort Chen, Xiangjun
collection PubMed
description 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.
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spelling pubmed-46007422015-10-21 Acidic phospholipids govern the enhanced activation of IgG-B cell receptor Chen, Xiangjun Pan, Weiling Sui, Yinqiang Li, Hua Shi, Xiaoshan Guo, Xingdong Qi, Hai Xu, Chenqi Liu, Wanli Nat Commun Article 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. Nature Pub. Group 2015-10-06 /pmc/articles/PMC4600742/ /pubmed/26440273 http://dx.doi.org/10.1038/ncomms9552 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Xiangjun
Pan, Weiling
Sui, Yinqiang
Li, Hua
Shi, Xiaoshan
Guo, Xingdong
Qi, Hai
Xu, Chenqi
Liu, Wanli
Acidic phospholipids govern the enhanced activation of IgG-B cell receptor
title Acidic phospholipids govern the enhanced activation of IgG-B cell receptor
title_full Acidic phospholipids govern the enhanced activation of IgG-B cell receptor
title_fullStr Acidic phospholipids govern the enhanced activation of IgG-B cell receptor
title_full_unstemmed Acidic phospholipids govern the enhanced activation of IgG-B cell receptor
title_short Acidic phospholipids govern the enhanced activation of IgG-B cell receptor
title_sort acidic phospholipids govern the enhanced activation of igg-b cell receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600742/
https://www.ncbi.nlm.nih.gov/pubmed/26440273
http://dx.doi.org/10.1038/ncomms9552
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