Interferon-driven deletion of antiviral B cells at the onset of chronic infection.
Fallet, Benedict; Narr, Kerstin; Ertuna, Yusuf I.; Remy, Melissa; 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 D.
[Article] Science Immunology. 1(4), October 21, 2016.

(Format: HTML, PDF)

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 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.

Copyright (C) 2016 by the American Association for the Advancement of Science