title: Interferon-driven deletion of antiviral B cells at the onset of chronic infection.
abstract: Inadequate antibody responses and perturbed B cell compartments represent hallmarks of persistent microbial infections, but the mechanisms whereby persisting pathogens suppress humoral immunity remain poorly defined. Using adoptive transfer experiments in the context of a chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, we have documented rapid depletion of virus-specific B cells that coincided with the early type I interferon response to infection. We found that the loss of activated B cells was driven by type I interferon (IFN-I) signaling to several cell types including dendritic cells, T cells and myeloid cells. Intriguingly, this process was independent of B cell-intrinsic IFN-I sensing and resulted from biased differentiation of naïve B cells into short-lived antibody-secreting cells. The ability to generate robust B cell responses was restored upon IFN-I receptor blockade or, partially, when experimentally depleting myeloid cells or the IFN-I-induced cytokines interleukin 10 and tumor necrosis factor alpha. We have termed this IFN-I-driven depletion of B cells "B cell decimation". Strategies to counter "B cell decimation" should thus help us better leverage humoral immunity in the combat against persistent microbial diseases.
authors.affiliation: Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
authors.forename: Benedict
authors.initials: B
authors.lastname: Fallet
authors.affiliation: Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Narr
authors.affiliation: Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
authors.forename: Yusuf I
authors.initials: YI
authors.lastname: Ertuna
authors.affiliation: Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
authors.forename: Melissa
authors.initials: M
authors.lastname: Remy
authors.affiliation: Department of Pathology and Immunology, Geneva Faculty of Medicine, 1211 Geneva 4, Switzerland.
authors.forename: Rami
authors.initials: R
authors.lastname: Sommerstein
authors.affiliation: Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
authors.forename: Karen
authors.initials: K
authors.lastname: Cornille
authors.affiliation: Department of Pathology and Immunology, Geneva Faculty of Medicine, 1211 Geneva 4, Switzerland.|Division of Clinical Pathology, University Hospital Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Kreutzfeldt
authors.affiliation: Department of Pathology and Immunology, Geneva Faculty of Medicine, 1211 Geneva 4, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Page
authors.affiliation: Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland.
authors.forename: Gert
authors.initials: G
authors.lastname: Zimmer
authors.affiliation: Department of Biomedicine, Bioinformatics Core Facility, University Hospital Basel, 4031 Basel, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Geier
authors.affiliation: Institute for Immunology, Department for Medical Microbiology and Hygiene, University Medical Center Freiburg, 79104 Freiburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Straub
authors.affiliation: Institute for Immunology, Department for Medical Microbiology and Hygiene, University Medical Center Freiburg, 79104 Freiburg, Germany.
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Pircher
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA.|Department of Immunology, University of Washington, Seattle, Washington, WA 98109, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Larimore
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA.|Department of Immunology, University of Washington, Seattle, Washington, WA 98109, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
authors.affiliation: Department of Pathology and Immunology, Geneva Faculty of Medicine, 1211 Geneva 4, Switzerland.|Division of Clinical Pathology, University Hospital Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.affiliation: Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Pinschewer