Acidic phospholipids govern the enhanced activation of IgG-B cell receptor.
Acidic phospholipids govern the enhanced activation of IgG-B cell receptor.
复制标题
酸性磷脂控制 IgG-B 细胞受体的增强激活。
DOI：
10.1038/ncomms9552
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发表时间：
2015-10-06
影响因子：
16.6
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Chen X;Pan W;Sui Y;Li H;Shi X;Guo X;Qi H;Xu C;Liu W
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 Ca2+ 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.
