Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Blood. 2013 May 16;121(20):4101-9. doi: 10.1182/blood-2012-10-465336. Epub 2013 Apr 4.
It is not known how naive B cells compute divergent chemoattractant signals of the T-cell area and B-cell follicles during in vivo migration. Here, we used two-photon microscopy of peripheral lymph nodes (PLNs) to analyze the prototype G-protein-coupled receptors (GPCRs) CXCR4, CXCR5, and CCR7 during B-cell migration, as well as the integrin LFA-1 for stromal guidance. CXCR4 and CCR7 did not influence parenchymal B-cell motility and distribution, despite their role during B-cell arrest in venules. In contrast, CXCR5 played a nonredundant role in B-cell motility in follicles and in the T-cell area. B-cell migration in the T-cell area followed a random guided walk model, arguing against directed migration in vivo. LFA-1, but not α4 integrins, contributed to B-cell motility in PLNs. However, stromal network guidance was LFA-1 independent, uncoupling integrin-dependent migration from stromal attachment. Finally, we observed that despite a 20-fold reduction of chemokine expression in virus-challenged PLNs, CXCR5 remained essential for B-cell screening of antigen-presenting cells. Our data provide an overview of the contribution of prototype GPCRs and integrins during naive B-cell migration and shed light on the local chemokine availability that these cells compute.
尚不清楚初始 B 细胞在体内迁移过程中如何计算 T 细胞区和 B 细胞滤泡的发散趋化因子信号。在这里，我们使用双光子显微镜分析了外周淋巴结（PLN）中初始 B 细胞迁移过程中的原型 G 蛋白偶联受体（GPCR）CXCR4、CXCR5 和 CCR7，以及用于基质导向的整合素 LFA-1。尽管 CXCR4 和 CCR7 在静脉中 B 细胞捕获过程中发挥作用，但它们并不影响实质 B 细胞的迁移和分布。相比之下，CXCR5 在滤泡和 T 细胞区的 B 细胞迁移中发挥非冗余作用。T 细胞区中的 B 细胞迁移遵循随机游走模型，这表明体内不存在定向迁移。LFA-1，但不是α4 整合素，有助于 PLN 中 B 细胞的迁移。然而，基质网络导向与 LFA-1 无关，它将整合素依赖性迁移与基质附着解耦。最后，我们观察到，尽管在受病毒挑战的 PLN 中趋化因子表达减少了 20 倍，CXCR5 仍然是 B 细胞对抗原呈递细胞进行筛选所必需的。我们的数据概述了原型 GPCR 和整合素在初始 B 细胞迁移中的作用，并阐明了这些细胞计算的局部趋化因子可用性。
