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Sci Immunol. 2016 Oct 21;1(4). pii: eaah6817. doi: 10.1126/sciimmunol.aah6817.

Interferon-driven deletion of antiviral B cells at the onset of chronic infection.

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Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
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.
Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland.
Department of Biomedicine, Bioinformatics Core Facility, University Hospital Basel, 4031 Basel, Switzerland.
Institute for Immunology, Department for Medical Microbiology and Hygiene, University Medical Center Freiburg, 79104 Freiburg, Germany.
Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA.
Department of Immunology, University of Washington, Seattle, Washington, WA 98109, USA.
Contributed equally


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.

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