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2018 ; 172
(3
): 517-533.e20
Nephropedia Template TP
gab.com Text
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English Wikipedia
Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially
Positioned NKT Cells
#MMPMID29249358
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 RP
; Barouch DH
; Shalek AK
; Bruckbauer A
; Strid J
; Batista FD
Cell
2018[Jan]; 172
(3
): 517-533.e20
PMID29249358
show ga
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.