Research ArticleINFECTIOUS DISEASES

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

Science Immunology  21 Oct 2016:
Vol. 1, Issue 4,
DOI: 10.1126/sciimmunol.aah6817

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B cells hoisted by their own petard: IFN-I

Certain pathogens, including HIV and hepatitis viruses, that lead to persistent infections are often associated with suboptimal antibody responses. Using LCMV infection in mice, Fallet et al., Moseman et al., and Sammicheli et al. report that up-regulation of type I interferon (IFN-I) in the early phase of infection is a key contributor to premature deletion of virus-specific B cells. Blockade of IFN-I prevents B cell deletion. Although the studies agree that IFN-I does not act directly on B cells, they found that distinct immune cells mediate IFN-I–dependent deletion of B cells, depending on the system examined. Targeting of the IFN-I pathway could be used to restore B cell responses during persistent viral infections in humans.

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 infection of mice, we have documented rapid depletion of virus-specific B cells that coincided with the early type I interferon (IFN-I) response to infection. We found that the loss of activated B cells was driven by IFN-I signaling to several cell types including dendritic cells, T cells, and myeloid cells. 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–α. 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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