title: Type I Interferon Impairs Specific Antibody Responses Early during Establishment of LCMV Infection.
abstract: Elicitation of type I interferon (IFN-I) has been shown to both enhance and impair cell-mediated immune responses in acute and persistent viral infections, respectively. Here, we show that, in addition to its effect on T cells, IFN-I drives impairment of specific antibody responses through interaction with B cells in the acute phase of lymphocytic choriomeningitis virus (LCMV) infection. This impairment was limited to the T cell-dependent B cell response and was associated with disruption of B cell follicles, development of hypergammaglobulinemia (HGG), and expansion of the T follicular helper cell population. Antigen-specific antibody responses were restored by ablation of IFN-I signaling through antibody-mediated IFN-I receptor blockade and B cell-specific IFN-I receptor knockout. Importantly, IFN-I receptor deficiency in B cells also accelerated the development of LCMV neutralizing antibodies and alleviated HGG. These results provide a potential therapeutic target toward efficient treatment measures that limit immunopathology in persistent viral infections.
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, QC , Canada.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Daugan
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, QC , Canada.
authors.forename: Armstrong
authors.initials: A
authors.lastname: Murira
authors.affiliation: Complex Traits Group, Department of Microbiology and Immunology, McGill University , Montréal, QC , Canada.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Mindt
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, QC , Canada.
authors.forename: Amélie
authors.initials: A
authors.lastname: Germain
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, QC , Canada.
authors.forename: Esther
authors.initials: E
authors.lastname: Tarrab
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, QC , Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lapierre
authors.affiliation: Complex Traits Group, Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; Complex Traits Group, Department of Physiology, McGill University, Montréal, QC, Canada.
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Fritz
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, QC , Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Lamarre
keywords: LCMV; antibody formation; immunopathology; interferon type I; neutralizing antibodies