Induction of optimal anti-viral neutralizing B cell responses by dendritic cells requires transport and release of virus particles in secondary lymphoid organs

Abstract

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.