Harwood Naomi E, Batista Facundo D
Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London, UK.
Curr Top Microbiol Immunol. 2009;334:153-77. doi: 10.1007/978-3-540-93864-4_7.
The appropriate activation of B cells is critical for the development of effective immune responses. B cell activation is initiated following the engagement of the B cell receptor (BCR) with specific antigen. The spatiotemporal characterization of the ensuing molecular and cellular events has been the subject of recent high-resolution imaging investigations. In this review we highlight information gathered thus far concerning the initial processes underlying the activation of B cells. First, we consider studies that have offered new insights into the early molecular events that occur within the B cell prior to formation of the immunological synapse. As such, BCR-microclusters formed on engagement with antigen have been identified as the sites of active signaling and assembly of "microsignalosomes." Furthermore, signaling through these "microsignalosomes" is propagated and enhanced through B cell spreading in response to membrane-antigen in a CD19-dependent manner. Finally, we discuss a number of multiphoton microscopy studies that have enabled dynamic characterization of the initial encounters between B cells and antigen in vivo. These investigations visualize the presentation of larger antigens to B cells via cell-mediated strategies, involving macrophages in the subcapsular sinus and dendritic cells in the paracortex.
B细胞的适当激活对于有效免疫反应的发展至关重要。B细胞受体（BCR）与特定抗原结合后启动B细胞激活。随后分子和细胞事件的时空特征一直是近期高分辨率成像研究的主题。在本综述中，我们重点介绍了迄今为止收集到的有关B细胞激活基础初始过程的信息。首先，我们考虑那些对免疫突触形成之前B细胞内发生的早期分子事件提供了新见解的研究。因此，与抗原结合时形成的BCR微簇已被确定为活性信号传导和“微信号体”组装的位点。此外，通过这些“微信号体”的信号传导通过B细胞响应膜抗原以CD19依赖性方式扩散而得以传播和增强。最后，我们讨论了一些多光子显微镜研究，这些研究能够动态表征体内B细胞与抗原之间的初始相遇。这些研究通过细胞介导的策略，包括被膜下窦中的巨噬细胞和副皮质中的树突状细胞，观察到较大抗原向B细胞的呈递。
