Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

Cell
Authors
Keywords
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.

Year of Publication
2018
Journal
Cell
Volume
172
Issue
3
Pages
517-533.e20
Date Published
2018 01 25
ISSN
1097-4172
DOI
10.1016/j.cell.2017.11.036
PubMed ID
29249358
PubMed Central ID
PMC5786505
Links
Grant list
Wellcome Trust / United Kingdom
UM1 AI100663 / AI / NIAID NIH HHS / United States
FC001035 / Cancer Research UK / United Kingdom
Medical Research Council / United Kingdom