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

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

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
Number of pages18
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Dahlgren, Plumb, Niss, Lahl, Brunak and Johansson-Lindbom.

    Research areas

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

ID: 315476778