Research ArticleINFECTIOUS DISEASES

Inflammatory monocytes hinder antiviral B cell responses

Science Immunology  21 Oct 2016:
Vol. 1, Issue 4,
DOI: 10.1126/sciimmunol.aah6789

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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 lymphocytic choriomeningitis virus 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

Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. We analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of draining lymph nodes, where they extensively interact with CD11b+Ly6Chi inflammatory monocytes. These myeloid cells were recruited to lymph nodes draining LCMV infection sites in a type I interferon– and CCR2-dependent fashion, and they suppressed antiviral B cell responses by virtue of their ability to produce nitric oxide. Depletion of inflammatory monocytes, inhibition of their lymph node recruitment, or impairment of their nitric oxide–producing ability enhanced LCMV-specific B cell survival and led to robust neutralizing antibody production. Our results identify inflammatory monocytes as critical gatekeepers that restrain antiviral B cell responses and suggest that certain viruses take advantage of these cells to prolong their persistence within the host.

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