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

Dahlgren, Madelene W.Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups (author)

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.

Plumb, Adam W.Technical University of Denmark (author)
Niss, KristofferUniversity of Copenhagen (author)
Lahl, KatharinaLund University,Lunds universitet,Virusrekognition,Forskargrupper vid Lunds universitet,Virus Recognition,Lund University Research Groups,Technical University of Denmark(Swepub:lu)med-kl2 (author)
Brunak, SørenUniversity of Copenhagen,Technical University of Denmark (author)
Johansson-Lindbom, BengtLund University,Lunds universitet,Adaptivt immunförsvar,Forskargrupper vid Lunds universitet,Adaptive Immunity,Lund University Research Groups,Technical University of Denmark(Swepub:lu)immt-bjo (author)
NeuroinflammationForskargrupper vid Lunds universitet (creator_code:org_t)

By the author/editor: Dahlgren, Madele ...; Plumb, Adam W.; Niss, Kristoffer; Lahl, Katharina; Brunak, Søren; Johansson-Lindbo ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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