Article ; Online: Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.
2017 Volume 172, Issue 3, Page(s) 517–533.e20
Abstract: ... for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas ... signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up ... reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical ...
| 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. |
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| MeSH term(s) | Animals ; B-Lymphocytes/immunology ; Chickens ; Dogs ; Germinal Center/cytology ; Germinal Center/immunology ; Humans ; Immunity, Innate ; Influenza, Human/immunology ; Interleukin-4/genetics ; Interleukin-4/metabolism ; Killer Cells, Natural/immunology ; Macaca ; Macrophages/immunology ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred C57BL ; Zika Virus Infection/immunology |
| Chemical Substances | Interleukin-4 (207137-56-2) |
| Language | English |
| Publishing date | 2017-12-14 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 187009-9 |
| ISSN | 1097-4172 ; 0092-8674 |
| ISSN (online) | 1097-4172 |
| ISSN | 0092-8674 |
| DOI | 10.1016/j.cell.2017.11.036 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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