Tsourkas Philippos K, Longo Marjorie L, Raychaudhuri Subhadip
Department of Biomedical Engineering, University of California, Davis, California 95616, USA.
Biophys J. 2008 Aug;95(3):1118-25. doi: 10.1529/biophysj.107.122564. Epub 2008 May 2.
B cell receptors have been shown to cluster at the intercellular junction between a B cell and an antigen-presenting cell in the form of a segregated pattern of B cell receptor/antigen complexes known as an immunological synapse. We use random walk-based theoretical arguments and Monte Carlo simulations to study the effect of diffusion of surface-bound molecules on B cell synapse formation. Our results show that B cell synapse formation is optimal for a limited range of receptor-ligand complex diffusion coefficient values, typically one-to-two orders of magnitude lower than the diffusion coefficient of free receptors. Such lower mobility of receptor-ligand complexes can significantly affect the diffusion of a tagged receptor or ligand in an affinity dependent manner, as the binding/unbinding of such receptor or ligand molecules crucially depends on affinity. Our work shows how single molecule tracking experiments can be used to estimate the order of magnitude of the diffusion coefficient of receptor-ligand complexes, which is difficult to measure directly in experiments due to the finite lifetime of receptor-ligand bonds. We also show how such antigen movement data at the single molecule level can provide insight into the B cell synapse formation mechanism. Thus, our results can guide further single molecule tracking experiments to elucidate the synapse formation mechanism in B cells, and potentially in other immune cells.
已证明B细胞受体以一种被称为免疫突触的B细胞受体/抗原复合物的分离模式，聚集在B细胞与抗原呈递细胞之间的细胞间连接处。我们使用基于随机游走的理论论证和蒙特卡罗模拟来研究表面结合分子的扩散对B细胞突触形成的影响。我们的结果表明，对于有限范围的受体-配体复合物扩散系数值，B细胞突触形成是最优的，该值通常比游离受体的扩散系数低一到两个数量级。受体-配体复合物如此低的迁移率可以以亲和力依赖的方式显著影响标记受体或配体的扩散，因为此类受体或配体分子的结合/解离关键取决于亲和力。我们的工作展示了如何利用单分子追踪实验来估计受体-配体复合物扩散系数的数量级，由于受体-配体键的有限寿命，该系数在实验中难以直接测量。我们还展示了单分子水平上的此类抗原运动数据如何能够深入了解B细胞突触形成机制。因此，我们的结果可以指导进一步的单分子追踪实验，以阐明B细胞以及潜在其他免疫细胞中的突触形成机制。
