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Type I Interferons ...
Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages
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- Dahlgren, Madelene W. (författare)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Plumb, Adam W. (författare)
- Technical University of Denmark
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- Niss, Kristoffer (författare)
- University of Copenhagen
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- Lahl, Katharina (författare)
- Lund University,Lunds universitet,Virusrekognition,Forskargrupper vid Lunds universitet,Virus Recognition,Lund University Research Groups,Technical University of Denmark
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- Brunak, Søren (författare)
- Technical University of Denmark,University of Copenhagen
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- Johansson-Lindbom, Bengt (författare)
- Lund University,Lunds universitet,Adaptivt immunförsvar,Forskargrupper vid Lunds universitet,Adaptive Immunity,Lund University Research Groups,Technical University of Denmark
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(creator_code:org_t)
- 2022-07-13
- 2022
- Engelska.
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Type I interferons (IFNs) are essential for antiviral immunity, appear to represent a key component of mRNA vaccine-adjuvanticity, and correlate with severity of systemic autoimmune disease. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood. 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 in B cells 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 divergent Th1 and Tfh cell-dependent pathways.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- antibody responses
- germinal center (GC) B cells
- IgG subclass antibodies
- Tfh cells
- Th1 cells
- Type I Interferons
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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