Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Fulltext
Final published version, 4.12 MB, PDF document
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 language | English |
---|---|
Article number | 932388 |
Journal | Frontiers in Immunology |
Volume | 13 |
Number of pages | 18 |
ISSN | 1664-3224 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:
Copyright © 2022 Dahlgren, Plumb, Niss, Lahl, Brunak and Johansson-Lindbom.
- antibody responses, germinal center (GC) B cells, IgG subclass antibodies, Tfh cells, Th1 cells, Type I Interferons
Research areas
ID: 315476778