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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Published: |
Elsevier
2018
|
| Online Access: | http://hdl.handle.net/1721.1/113555 |
| _version_ | 1811006124517752832 |
|---|---|
| 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. Bruckbauer, Andreas Strid, Jessica Batista, Facundo D. Shalek, Alexander K |
| author2 | Institute for Medical Engineering and Science |
| author_facet | Institute for Medical Engineering and Science 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. Bruckbauer, Andreas Strid, Jessica Batista, Facundo D. Shalek, Alexander K |
| author_sort | Gaya, Mauro |
| collection | MIT |
| 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. 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 |
| first_indexed | 2024-09-23T16:47:07Z |
| format | Article |
| id | mit-1721.1/113555 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:47:07Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1135552022-09-29T21:29:54Z 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. Bruckbauer, Andreas Strid, Jessica Batista, Facundo D. Shalek, Alexander K Institute for Medical Engineering and Science Shalek, Alexander K 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 2018-02-09T16:19:48Z 2018-02-09T16:19:48Z 2017-12 2017-09 2018-02-05T17:43:40Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/113555 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) http://dx.doi.org/10.1016/j.cell.2017.11.036 Cell Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | 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. Bruckbauer, Andreas Strid, Jessica Batista, Facundo D. Shalek, Alexander K 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 |
| url | http://hdl.handle.net/1721.1/113555 |
| work_keys_str_mv | AT gayamauro initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT barralpatricia initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT burbagemarianne initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT aggarwalshweta initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT montanerbeatriz initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT warrennaviaandrew initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT aidmalika initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT tsuicarlson initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT maldonadopaula initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT nairusha initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT ghneimkhader initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT fallonpadraicg initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT sekalyrafickpierre initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT barouchdanh initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT bruckbauerandreas initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT stridjessica initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT batistafacundod initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells AT shalekalexanderk initiationofantiviralbcellimmunityreliesoninnatesignalsfromspatiallypositionednktcells |