Ludewig B, Maloy K J, López-Macías C, Odermatt B, Hengartner H, Zinkernagel R M
Institute of Experimental Immunology, Zürich, Switzerland.
Eur J Immunol. 2000 Jan;30(1):185-96. doi: 10.1002/1521-4141(200001)30:1<185::AID-IMMU185>3.0.CO;2-L.
Dendritic cells (DC) are sentinels of the immune system, transporting antigens from the periphery to secondary lymphoid organs. This study investigates the interactions of DC with B cells for the induction of anti-viral neutralizing antibody responses. Using the vesicular stomatitis virus glycoprotein (VSV-G) as a model antigen, we show that DC contain infection with cytopathic VSV in the presence of a functional IFN system, facilitating transport and release of low levels of live virus in secondary lymphoid organs. DC exposed to live virus induced efficient neutralizing anti-viral B cell responses. In contrast, DC transporting UV-inactivated viral antigens were poor activators of anti-viral B cells, although they were capable of very efficiently inducing virus-specific Th cells. Transgenic DC expressing a membrane-bound form of VSV-G induced neutralizing B cell responses; however, this DC-induced, Th-dependent B cell response was significantly slower than the anti-viral B cell response induced by DC infected with live VSV, and was strongly dependent on concomitant priming of T help. These results suggest that DC may play a double role during infection with cytopathic virus: they transport and release live virus in secondary lymphoid tissues for optimal direct B cell induction and offer MHC class II-associated determinants for induction of T help.
树突状细胞(DC)是免疫系统的哨兵,负责将抗原从外周运输至二级淋巴器官。本研究调查了DC与B细胞之间的相互作用,以诱导抗病毒中和抗体反应。以水泡性口炎病毒糖蛋白(VSV-G)作为模型抗原,我们发现,在存在功能性干扰素系统的情况下,DC含有感染性的细胞病变型VSV,这有助于在二级淋巴器官中运输和释放低水平的活病毒。暴露于活病毒的DC可诱导有效的抗病毒B细胞中和反应。相比之下,运输紫外线灭活病毒抗原的DC虽然能够非常有效地诱导病毒特异性Th细胞,但却是抗病毒B细胞的低效激活剂。表达膜结合形式VSV-G的转基因DC可诱导中和B细胞反应;然而,这种由DC诱导的、Th细胞依赖性的B细胞反应明显慢于感染活VSV的DC所诱导的抗病毒B细胞反应,并且强烈依赖于伴随的T辅助细胞启动。这些结果表明,DC在细胞病变型病毒感染过程中可能发挥双重作用:它们在二级淋巴组织中运输和释放活病毒,以实现最佳的直接B细胞诱导,并提供与MHC II类相关的决定簇以诱导T辅助细胞。