Initiation of antiviral B cell Immunity relies on innate signals from spatially positioned NKT cells
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up to 70% of the total IL-4-producing cells during the initial stages of infection. Importantly, the requirement of this innate immunity arm appears to be evolutionarily conserved because early NKT and IL-4 gene signatures also positively correlate with the levels of neutralizing antibodies in Zika-virus-infected macaques. In conclusion, our data support a model wherein a pre-TfH wave of IL-4 secreted by interfollicular NKT cells triggers the seeding of germinal center cells and serves as an innate link between viral infection and B cell immunity.
Date Issued
2017-12-12
Date Acceptance
2017-11-20
Citation
Cell, 2017, 172 (3), pp.517-533.e20
ISSN
0092-8674
Publisher
Elsevier
Start Page
517
End Page
533.e20
Journal / Book Title
Cell
Volume
172
Issue
3
Copyright Statement
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Wellcome Trust
Identifier
PII: S0092-8674(17)31387-9
Grant Number
100999/Z/13/Z
Subjects
B cells
CXCR3
IL-4
NKT cells
Zika virus
germinal center seeding
influenza
lymph node
macrophages
viral infection
Publication Status
Published online