title: Early type I interferon-mediated signals on B cells specifically enhance antiviral humoral responses.
abstract: Type I interferons (IFN-I) limit viral spread by inducing antiviral genes in infected target cells and by shaping the adaptive response through induction of additional cytokines. Vesicular stomatitis virus (VSV) efficiently triggers the production of IFN-I in mice, and it is suggested that IFN-alpha is induced after binding of VSV to TLR7 in infected cells. Our study with virus-specific B cell receptor-transgenic mice demonstrates here that IFN-I directly fuel early humoral immune responses in vivo. VSV-specific B cells that lacked IFN-alpha/beta receptors were considerably impaired in plasma cell formation and in generating antiviral IgM. At low viral titers, production of IFN-alpha following VSV infection was independent of TLR7-mediated signals. Interestingly, however, TLR7 ligation in B cells increased the formation of early antiviral IgM. These findings indicate that IFN-alpha-mediated augmentation of specific B cell responses is a partially TLR7- and virus dose-dependent mechanism.
authors.affiliation: Institute of Experimental Immunology, University Hospital Zurich, Zurich, Switzerland. katja.fink@usz.ch
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
authors.forename: Nataly
authors.initials: N
authors.lastname: Manjarrez-Orduno
authors.forename: Tobias
authors.initials: T
authors.lastname: Junt
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Senn
authors.forename: Martin
authors.initials: M
authors.lastname: Holdener
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: Hans
authors.initials: H
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D007370:Interferon Type I / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D017471:Receptors, Interferon; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D053633:Receptor, Interferon alpha-beta