A balance of Bruton's tyrosine kinase and SHIP activation regulates B cell receptor cluster formation by controlling actin remodeling.
A balance of Bruton's tyrosine kinase and SHIP activation regulates B cell receptor cluster formation by controlling actin remodeling.
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DOI：
10.4049/jimmunol.1100157
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Song W
中科院分区：
文献类型：
--
作者：
Liu C;Miller H;Hui KL;Grooman B;Bolland S;Upadhyaya A;Song W
启动B细胞活化的B细胞受体（BCR）的活化是由抗原诱导的自聚集和细胞表面的受体簇集触发的。虽然已知抗原诱导的肌动蛋白重组参与了对膜相关抗原的BCR聚集，但将肌动蛋白重组与BCR活化联系起来的潜在机制仍然未知。在这里，我们表明，刺激性布鲁顿的酪氨酸激酶（Btk）和抑制性SH 2-含有肌醇-5磷酸酶-1（SHIP-1）是必需的有效的BCR自我聚集。在Btk缺陷型B细胞中，与野生型B细胞中观察到的相比，响应于抗原栓系的脂质双层的BCR聚集成簇和B细胞扩散的幅度显著降低。在SHIP-1−/− B细胞中，虽然表面BCR聚集成微簇，但BCR簇的向心运动和生长受到抑制，B细胞扩散增加。SHIP−/− B细胞中的持久BCR微簇比合并的BCR簇表现出更高水平的信号传导。与Btk缺陷B细胞中肌动蛋白重塑的抑制相反，SHIP-1−/− B细胞中肌动蛋白聚合、F-肌动蛋白积累和WASP磷酸化以Btk依赖性方式增强。因此，正信号和负信号之间的平衡通过控制肌动蛋白重塑来调节细胞表面BCR的时空组织，这可能调节BCR的信号转导。这项研究表明，BCR信号和肌动蛋白细胞骨架之间的一种新的反馈回路。
The activation of the B-cell receptor (BCR), which initiates B-cell activation, is triggered by antigen-induced self-aggregation and clustering of receptors at the cell surface. While antigen-induced actin reorganization is known to be involved in BCR clustering in response to membrane-associated antigen, the underlying mechanism that links actin reorganization to BCR activation remains unknown. Here we show that both the stimulatory Bruton’s tyrosine kinase (Btk) and the inhibitory SH2-containing inositol-5 phosphatase-1 (SHIP-1) are required for efficient BCR self-aggregation. In Btk-deficient B cells, the magnitude of BCR aggregation into clusters and B-cell spreading in response to antigen-tethered lipid bilayer is drastically reduced, compared to that observed in wild type B-cells. In SHIP-1−/− B-cells, while surface BCRs aggregate into microclusters, the centripetal movement and growth of BCR clusters are inhibited and B-cell spreading is increased. The persistent BCR microclusters in SHIP−/− B-cells exhibit higher levels of signaling than merged BCR clusters. Contrast to the inhibition of actin remodeling in Btk-deficient B-cells, actin polymerization, F-actin accumulation, and WASP phosphorylation are enhanced in SHIP-1−/− B-cells in a Btk-dependent manner. Thus, a balance between positive and negative signaling regulates the spatiotemporal organization of the BCR at the cell surface by controlling actin remodeling, which potentially regulates the signal transduction of the BCR. This study suggests a novel feedback loop between BCR signaling and the actin cytoskeleton.
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DOI：
10.4049/jimmunol.0902334
发表时间：
2010-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Liu W;Won Sohn H;Tolar P;Meckel T;Pierce SK
通讯作者：
Pierce SK
影响因子：
32.4
作者：
Arana, Eloisa;Vehlow, Anne;Batista, Facundo D.
通讯作者：
Batista, Facundo D.
影响因子：
32.4
作者：
Bolland, S;Pearse, RN;Ravetch, JV
通讯作者：
Ravetch, JV
影响因子：
32.4
作者：
Liu W;Meckel T;Tolar P;Sohn HW;Pierce SK
通讯作者：
Pierce SK
影响因子：
20.3
作者：
Meyer-Bahlburg A;Becker-Herman S;Humblet-Baron S;Khim S;Weber M;Bouma G;Thrasher AJ;Batista FD;Rawlings DJ
通讯作者：
Rawlings DJ