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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.

Author information

1
Department of Biomedicine, Division of Experimental Virology, University of Basel, 4003 Basel, Switzerland.
2
Department of Pathology and Immunology, Geneva Faculty of Medicine, 1211 Geneva 4, Switzerland.
3
Division of Clinical Pathology, University Hospital Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
4
Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland.
5
Department of Biomedicine, Bioinformatics Core Facility, University Hospital Basel, 4031 Basel, Switzerland.
6
Institute for Immunology, Department for Medical Microbiology and Hygiene, University Medical Center Freiburg, 79104 Freiburg, Germany.
7
Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA.
8
Department of Immunology, University of Washington, Seattle, Washington, WA 98109, USA.
#
Contributed equally

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.

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