Ligand Mobility Regulates B Cell Receptor Clustering and Signaling Activation
Ligand Mobility Regulates B Cell Receptor Clustering and Signaling Activation
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DOI：
10.1016/j.bpj.2013.10.043
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发表时间：
2014-01-07
影响因子：
3.4
通讯作者：
Upadhyaya, Arpita
中科院分区：
文献类型：
--
作者：
Ketchum, Christina;Miller, Heather;Upadhyaya, Arpita
抗原与B细胞受体（BCR）的结合诱导受体聚集、细胞扩散和信号微簇的形成，从而触发B细胞活化。尽管已经很好地研究了控制早期B细胞信号传导的生物化学途径，但是抗原的物理性质（例如抗原迁移率）的作用尚未得到充分研究。我们研究了B细胞与包被在玻璃上或拴系在平面脂质双层表面上的BCR配体的相互作用，以研究B细胞对非移动的和移动的配体的反应差异。使用高分辨率全内反射荧光（TIRF）显微镜的活细胞，我们遵循的运动和空间组织的BCR集群和相关的信号。尽管任一表面上的配体都能够交联BCR并诱导成簇，但与移动的配体相互作用的B细胞显示出比与非移动的配体相互作用的细胞更大的信号传导。定量分析表明，移动的配体使BCR集群移动更远，更有效地合并比im移动的配体。受体簇的物理重组的这些差异与肌动蛋白重塑的差异有关。扰动实验表明，动态肌动蛋白细胞骨架积极重组受体簇。这些结果表明配体迁移率是调节B细胞信号传导的重要参数。
Antigen binding to the B cell receptor (BCR) induces receptor clustering, cell spreading, and the formation of signaling microclusters, triggering B cell activation. Although the biochemical pathways governing early B cell signaling have been well studied, the role of the physical properties of antigens, such as antigen mobility, has not been fully examined. We study the interaction of B cells with BCR ligands coated on glass or tethered to planar lipid bilayer surfaces to investigate the differences in B cell response to immobile and mobile ligands. Using high-resolution total internal reflection fluorescence (TIRF) microscopy of live cells, we followed the movement and spatial organization of BCR clusters and the associated signaling. Although ligands on either surface were able to cross-link BCRs and induce clustering, B cells interacting with mobile ligands displayed greater signaling than those interacting with immobile ligands. Quantitative analysis revealed that mobile ligands enabled BCR clusters to move farther and merge more efficiently than immobile ligands. These differences in physical reorganization of receptor clusters were associated with differences in actin remodeling. Perturbation experiments revealed that a dynamic actin cytoskeleton actively reorganized receptor clusters. These results suggest that ligand mobility is an important parameter for regulating B cell signaling.