title: 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.
authors.affiliation: Institute of Experimental Immunology, Zürich, Switzerland. Ludewigb@pathol.unizh.ch
authors.forename: B
authors.initials: B
authors.lastname: Ludewig
authors.forename: K J
authors.initials: KJ
authors.lastname: Maloy
authors.forename: C
authors.initials: C
authors.lastname: López-Macías
authors.forename: B
authors.initials: B
authors.lastname: Odermatt
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000502:physiology* / Q000821:virology; D018858:Germinal Center / Q000502:physiology; D007156:Immunologic Memory; D007372:Interferons / Q000502:physiology; D008221:Lymphoid Tissue / Q000821:virology*; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D007372:Interferons