B cell antigen receptor-induced Rac1 activation and Rac1-dependent spreading are impaired in transitional immature B cells due to levels of membrane cholesterol
B cell antigen receptor-induced Rac1 activation and Rac1-dependent spreading are impaired in transitional immature B cells due to levels of membrane cholesterol
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DOI：
10.4049/jimmunol.179.7.4464
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Monroe, John G.
中科院分区：
文献类型：
--
作者：
Brezski, Randall J.;Monroe, John G.
成熟和过渡性未成熟B细胞对bcr的反应在生化和功能水平上都存在差异。在这项研究中，我们发现在成熟的B细胞中，BCR信号可以触发Vav磷酸化和Rac1激活。此外，我们证明，尽管下游肌动蛋白依赖的BCR封顶与Rac1激活无关，但肌动蛋白依赖的膜褶皱和细胞扩散是Rac1依赖的过程。相比之下，BCR诱导的Vav磷酸化和Rac1激活在移行性未成熟B细胞中受损，导致肌动蛋白聚合依赖的扩散和膜褶皱缺陷，而Rac1独立的BCR覆盖保持完整。由于过渡性未成熟小鼠B细胞维持较低的稳态质膜胆固醇水平，我们将其水平提高到成熟B细胞的水平，发现bcr诱导的Rac1激活和Rac1依赖的膜褶皱和细胞扩散得以恢复。这些研究提供了B细胞胆固醇水平与下游细胞信号传导过程之间的直接联系。
The BCR-triggered responses of mature and transitional immature B cells differ at both the biochemical and functional level. In this study, we show that in mature B cells, BCR signaling triggers Vav phosphorylation and Rac1 activation. Furthermore, we demonstrate that although downstream actin-dependent BCR capping is independent of Rac1 activation, actin-dependent membrane ruffling and cell spreading are Rac1-dependent processes. In contrast, BCR-induced Vav phosphorylation and Rac1 activation is impaired in transitional immature B cells, resulting in defects in actin polymerization-dependent spreading and membrane ruffling while Rac1-independent BCR capping remains intact. Because transitional immature murine B cells maintain lower steady-state levels of plasma membrane cholesterol, we augmented their levels to that of mature B cells and found that BCR-induced Rac1 activation and Rac1-dependent membrane ruffling and cell spreading were restored. These studies provide a direct link between B cell cholesterol levels and downstream cellular signaling processes.