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Initiation of antiviral B cell Immunity relies on innate signals from spatially positioned NKT cells

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Title: Initiation of antiviral B cell Immunity relies on innate signals from spatially positioned NKT cells
Authors: Gaya, M
Barral, P
Burbage, M
Aggarwal, S
Montaner, B
Warren Navia, A
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
Item Type: Journal Article
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.
Issue Date: 12-Dec-2017
Date of Acceptance: 20-Nov-2017
URI: http://hdl.handle.net/10044/1/55577
DOI: 10.1016/j.cell.2017.11.036
ISSN: 0092-8674
Publisher: Elsevier
Start Page: 517
End Page: 533.e20
Journal / Book Title: Cell
Volume: 172
Issue: 3
Copyright Statement: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 100999/Z/13/Z
Keywords: B cells
CXCR3
IL-4
NKT cells
Zika virus
germinal center seeding
influenza
lymph node
macrophages
viral infection
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
KILLER T-CELLS
LYMPH-NODES
IN-VIVO
ANTIBODY-RESPONSES
IL-4 PRODUCTION
COGNATE HELP
ANTIGEN
ACTIVATION
MICE
INFECTION
B cells
CXCR3
IL-4
NKT cells
Zika virus
germinal center seeding
influenza
lymph node
macrophages
viral infection
Animals
B-Lymphocytes
Chickens
Dogs
Germinal Center
Humans
Immunity, Innate
Influenza, Human
Interleukin-4
Killer Cells, Natural
Macaca
Macrophages
Madin Darby Canine Kidney Cells
Mice
Mice, Inbred C57BL
Zika Virus Infection
Germinal Center
B-Lymphocytes
Killer Cells, Natural
Macrophages
Animals
Mice, Inbred C57BL
Chickens
Dogs
Macaca
Humans
Mice
Interleukin-4
Influenza, Human
Immunity, Innate
Madin Darby Canine Kidney Cells
Zika Virus Infection
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published online
Appears in Collections:Department of Immunology and Inflammation
National Heart and Lung Institute
Faculty of Medicine