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

Fallet, Benedict; Narr, Kerstin; Ertuna, Yusuf I; Remy, Mélissa; Sommerstein, Rami; Cornille, Karen; Kreutzfeldt, Mario; Page, Nicolas; Zimmer, Gert; Geier, Florian; Straub, Tobias; Pircher, Hanspeter; Larimore, Kevin; Greenberg, Philip D; Merkler, Doron; Pinschewer, Daniel

doi:10.1126/sciimmunol.aah6817

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Title		Interferon-driven deletion of antiviral B cells at the onset of chronic infection
Authors		Fallet, Benedict Narr, Kerstin Ertuna, Yusuf I Remy, Mélissa Sommerstein, Rami Cornille, Karen Kreutzfeldt, Mario Page, Nicolas Zimmer, Gert Geier, Florian Straub, Tobias Pircher, Hanspeter Larimore, Kevin Greenberg, Philip D Merkler, Doron Pinschewer, Daniel show all authors [1 - 16]
Published in		Science Immunology. 2016, vol. 1, no. 4
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.
Identifiers		DOI: 10.1126/sciimmunol.aah6817 PMID: 27872905
Full text		Article (Accepted version) (2.8 MB) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		La Sclérose en plaques (908)
Citation (ISO format)		FALLET, Benedict et al. Interferon-driven deletion of antiviral B cells at the onset of chronic infection. In: Science immunology, 2016, vol. 1, n° 4. doi: 10.1126/sciimmunol.aah6817 https://archive-ouverte.unige.ch/unige:94180