Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
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Author(s)
Gaya, Mauro
Barral, Patricia
Burbage, Marianne
Aggarwal, Shweta
Montaner, Beatriz
Warren Navia, Andrew
Aid, Malika
Tsui, Carlson
Maldonado, Paula
Nair, Usha
Date Issued
December 2017
Journal
Cell
Publisher
Elsevier
Citation
Gaya, Mauro et al. “Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.” Cell 172, 3 (January 2018): 517–533 © 2017 The Author(s)
Version
Final published version
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. NKT cells are required for the initial formation of germinal centers and production of effective neutralizing antibody responses against viruses. Keywords: NKT cells; B cells; macrophages; germinal center seeding; IL-4;
viral infection; influenza; Zika virus; lymph node; CXCR3
MIT Department
Institute for Medical Engineering and Science
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2017.11.036
