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

TitleInitiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.
Publication TypeJournal Article
Year of Publication2018
AuthorsGaya M, Barral P, Burbage M, Aggarwal S, Montaner B, Navia AWarren, Aid M, Tsui C, Maldonado P, Nair U, Ghneim K, Fallon PG, Sekaly R-P, Barouch DH, Shalek AK, Bruckbauer A, Strid J, Batista FD
JournalCell
Volume172
Issue3
Pagination517-533.e20
Date Published2018 Jan 25
ISSN1097-4172
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.

DOI10.1016/j.cell.2017.11.036
Alternate JournalCell
PubMed ID29249358
PubMed Central IDPMC5786505
Grant List / / Wellcome Trust / United Kingdom
UM1 AI100663 / AI / NIAID NIH HHS / United States
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