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

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 ge...

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Autores principales: Gaya, Mauro, Barral, Patricia, Burbage, Marianne, Aggarwal, Shweta, Montaner, Beatriz, Warren Navia, Andrew, Aid, Malika, Tsui, Carlson, Maldonado, Paula, Nair, Usha, Ghneim, Khader, Fallon, Padraic G., Sekaly, Rafick-Pierre, Barouch, Dan H., Shalek, Alex K., Bruckbauer, Andreas, Strid, Jessica, Batista, Facundo D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786505/
https://www.ncbi.nlm.nih.gov/pubmed/29249358
http://dx.doi.org/10.1016/j.cell.2017.11.036
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author Gaya, Mauro
Barral, Patricia
Burbage, Marianne
Aggarwal, Shweta
Montaner, Beatriz
Warren Navia, Andrew
Aid, Malika
Tsui, Carlson
Maldonado, Paula
Nair, Usha
Ghneim, Khader
Fallon, Padraic G.
Sekaly, Rafick-Pierre
Barouch, Dan H.
Shalek, Alex K.
Bruckbauer, Andreas
Strid, Jessica
Batista, Facundo D.
author_facet Gaya, Mauro
Barral, Patricia
Burbage, Marianne
Aggarwal, Shweta
Montaner, Beatriz
Warren Navia, Andrew
Aid, Malika
Tsui, Carlson
Maldonado, Paula
Nair, Usha
Ghneim, Khader
Fallon, Padraic G.
Sekaly, Rafick-Pierre
Barouch, Dan H.
Shalek, Alex K.
Bruckbauer, Andreas
Strid, Jessica
Batista, Facundo D.
author_sort Gaya, Mauro
collection PubMed
description 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.
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spelling pubmed-57865052018-01-29 Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells Gaya, Mauro Barral, Patricia Burbage, Marianne Aggarwal, Shweta Montaner, Beatriz Warren Navia, Andrew Aid, Malika Tsui, Carlson Maldonado, Paula Nair, Usha Ghneim, Khader Fallon, Padraic G. Sekaly, Rafick-Pierre Barouch, Dan H. Shalek, Alex K. Bruckbauer, Andreas Strid, Jessica Batista, Facundo D. Cell Article 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. Cell Press 2018-01-25 /pmc/articles/PMC5786505/ /pubmed/29249358 http://dx.doi.org/10.1016/j.cell.2017.11.036 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gaya, Mauro
Barral, Patricia
Burbage, Marianne
Aggarwal, Shweta
Montaner, Beatriz
Warren Navia, Andrew
Aid, Malika
Tsui, Carlson
Maldonado, Paula
Nair, Usha
Ghneim, Khader
Fallon, Padraic G.
Sekaly, Rafick-Pierre
Barouch, Dan H.
Shalek, Alex K.
Bruckbauer, Andreas
Strid, Jessica
Batista, Facundo D.
Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
title Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
title_full Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
title_fullStr Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
title_full_unstemmed Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
title_short Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
title_sort initiation of antiviral b cell immunity relies on innate signals from spatially positioned nkt cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786505/
https://www.ncbi.nlm.nih.gov/pubmed/29249358
http://dx.doi.org/10.1016/j.cell.2017.11.036
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