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

Fallet, Benedict; Narr, Kerstin; Ertuna, Yusuf I; Remy, Melissa; Sommerstein, R.; Cornille, Karen; Kreutzfeldt, Mario; Page, Nicolas; Zimmer, Gert; Geier, Florian; Straub, Tobias; Pircher, Hanspeter; Larimore, Kevin; Greenberg, Philip D; Merkler, Doron; Pinschewer, Daniel D (2016). Interferon-driven deletion of antiviral B cells at the onset of chronic infection. Science immunology, 1(4) American Association for the Advancement of Science 10.1126/sciimmunol.aah6817

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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 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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