Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages

Madelene W. Dahlgren, Adam W. Plumb, Kristoffer Niss, Katharina Lahl, Søren Brunak, Bengt Johansson-Lindbom

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number932388
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 2022 Jul 13

Subject classification (UKÄ)

  • Immunology in the medical area

Free keywords

  • antibody responses
  • germinal center (GC) B cells
  • IgG subclass antibodies
  • Tfh cells
  • Th1 cells
  • Type I Interferons

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