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| Status |
Public on Jul 08, 2022 |
| Title |
Type I interferons promote germinal centers through B cell intrinsic signaling and dendritic cell dependent Th1 and Tfh cell lineages |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Type I interferons (IFNs) play an essential role in antiviral immunity, correlate with severity of systemic autoimmune disease, and are likely to represent a key component of mRNA vaccine-adjuvanticity. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood due to pleiotropic effects in multiple cell types. 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-g induces T-bet expression and IgG2c isotype switching 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 parallel Th1 and Tfh cell-dependent pathways.
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| Overall design |
mRNA sequencing of sorted IFNAR KO, IFNgR KO and WT splenic GC B cells at D8 after immunization with poly I:C and ovalbumin
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| Contributor(s) |
Johansson-Lindbom B, Plumb AW |
| Citation(s) |
35911733 |
| |
| Submission date |
Apr 26, 2022 |
| Last update date |
Aug 03, 2022 |
| Contact name |
Bengt Johansson-Lindbom |
| E-mail(s) |
bengt.johansson_lindbom@med.lu.se
|
| Organization name |
Lund University
|
| Department |
Adaptive Immunity
|
| Street address |
BMC D1421b
|
| City |
Lund |
| ZIP/Postal code |
22100 |
| Country |
Sweden |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA832211 |
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