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...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2015-10, Vol.6 (1), p.8552-8552, Article 8552
Main Authors: Chen, Xiangjun, Pan, Weiling, Sui, Yinqiang, Li, Hua, Shi, Xiaoshan, Guo, Xingdong, Qi, Hai, Xu, Chenqi, Liu, Wanli
Format: Article
Language:English
Subjects:
101/6
14
14/19
14/33
42
631/250/1619/40
631/45/287/1194
631/80/86
96
Animals
B-Lymphocytes - immunology
Calcium - metabolism
Humanities and Social Sciences
Humans
Immunoglobulin G - chemistry
Immunoglobulin G - genetics
Immunoglobulin G - immunology
Lymphocyte Activation
multidisciplinary
Phospholipids - chemistry
Phospholipids - immunology
Receptors, Antigen, B-Cell - genetics
Receptors, Antigen, B-Cell - immunology
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Adaptive immunity is the memory of previously experienced pathogens, where B cells establish a rapid antibody response upon IgG-B cell receptor activation. Here, Chen et al . show that sequestration of the cytoplasmic domain of mIgG by plasma membrane phospholipids prevents inappropriate activation of IgG-BCR signalling.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms9552