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

[img]
Preview
Text
emss-70441.pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (2MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Zimmer, Gert

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health

ISSN:

2470-9468

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

07 Jul 2017 13:48

Last Modified:

07 Jul 2017 13:48

Publisher DOI:

10.1126/sciimmunol.aah6817

PubMed ID:

27872905

BORIS DOI:

10.7892/boris.96170

URI:

https://boris.unibe.ch/id/eprint/96170

Actions (login required)

Edit item Edit item
Provide Feedback