Interferon-driven Deletion of Antiviral B Cells at the Onset of Chronic Infection

Fallet, Benedict and Narr, Kerstin and Ertuna, Yusuf I. and Remy, Melissa and Sommerstein, Rami and Cornille, Karen and Kreutzfeldt, Mario and Page, Nicolas and Zimmer, Gert and Geier, Florian and Straub, Tobias and Pircher, Hanspeter and Larimore, Kevin and Greenberg, Philip D. and Merkler, Doron and Pinschewer, Daniel D.. (2016) Interferon-driven Deletion of Antiviral B Cells at the Onset of Chronic Infection. Science Immunology, 1 (4). eaah6817.

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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 naive 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel and Cornille, Karen and Fallet, Bénédict
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for the Advancement of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 May 2020 09:47
Deposited On:25 May 2020 09:47

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