期刊
CELL REPORTS
卷 21, 期 9, 页码 2541-2557出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.10.117
关键词
-
类别
资金
- National Science Foundation China [81730043, 81422020, 81621002]
- Ministry of Science and Technology of China [2014CB542500]
The growth of B cell receptor (BCR) microclusters upon antigen stimulation drives B cell activation. Here, we show that PI3K-mediated PIP3 production is required for the growth of BCR microclusters. This growth is likely inhibited by PTEN and dependent on its plasma membrane binding and lipid phosphatase activities. Mechanistically, we find that PIP3-dependent recruitment and activation of a guanine nucleotide exchange factor, Dock2, is required for the sustained growth of BCR microclusters through remodeling of the F-actin cytoskeleton. As a consequence, Dock2 deficiency significantly disrupts the structure of the B cell immunological synapse. Finally, we find that primary B cells from systemic lupus erythematosus (SLE) patients exhibit more prominent BCR and PI3K microclusters than B cells from healthy controls. These results demonstrate the importance of a PI3K- and PTEN-governed PIP2 and PIP3 equilibrium in regulating the activation of B cells through Dock2-controlled growth of BCR microclusters.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据