| Property | Value |
|---|
|
?:abstract
|
-
Type I interferons (IFNs) play an essential role in antiviral immunity, correlate with severity of systemic autoimmune disease, and are likely to represent a key component of mRNA vaccine-adjuvanticity. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood due to pleiotropic effects in multiple cell types. Here, we demonstrate that a succinct type I IFN response promotes GC formation and associated IgG subclass distribution primarily through signaling in cDCs and B cells. Type I IFN signaling in cDCs, distinct from cDC1, stimulates development of separable Tfh and Th1 cell subsets. However, Th cell-derived IFN-γ induces T-bet expression and IgG2c isotype switching prior to this bifurcation and has no evident effects once GCs and bona fide Tfh cells developed. This pathway acts in synergy with early B cell-intrinsic type I IFN signaling, which reinforces T-bet expression in B cells and leads to a selective amplification of the IgG2c+ GC B cell response. Despite the strong Th1 polarizing effect of type I IFNs, the Tfh cell subset develops into IL-4 producing cells that control the overall magnitude of the GCs and promote generation of IgG1 + GC B cells. Thus, type I IFNs act on B cells and cDCs to drive GC formation and to coordinate IgG subclass distribution through parallel Th1 and Tfh cell-dependent pathways.
|
|
is
?:annotates
of
|
|
|
?:creator
|
|
|
?:doi
|
|
|
?:doi
|
-
10.1101/2020.11.20.390625
|
|
?:externalLink
|
|
|
?:journal
|
|
|
?:license
|
|
|
?:pdf_json_files
|
-
document_parses/pdf_json/32a87b729d1c29e4080c5ed56ae4e58456df3abd.json
|
|
?:publication_isRelatedTo_Disease
|
|
|
is
?:relation_isRelatedTo_publication
of
|
|
|
?:sha_id
|
|
|
?:source
|
|
|
?:title
|
-
Type I interferons promote germinal centers through B cell intrinsic signaling and dendritic cell dependent Th1 and Tfh cell lineages
|
|
?:type
|
|
|
?:year
|
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}