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| Status |
Public on May 14, 2020 |
| Title |
IL-23 promotes a coordinated B-cell germinal center program for class-switch recombination to IgG2b in BXD2 mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
IL-23 promotes autoimmune disease including Th17 CD4 T-cell development and autoantibody (autoAb) production. Here, we show that a deficiency of the p19 component of IL-23 in autoimmune BXD2 (BXD2-p19−/−) mice leads to an imbalance of the follicular T-helper cell program with a shift from Tfh-IL-17 to Tfh-IFN-ɣ. Although the germinal center (GC) size and number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) program in the GC B cells, leading to a lower serum levels of IgG2b. Single cell transcriptomics analysis revealed that while GC B cell expression of Ifngr1 and Il21r genes exhibited a synchronized expression pattern with plasma cell program genes, Il17ra exhibited a synchronized expression pattern with pre-plasmablast GC program genes. Down-regulation of Ighg2b in BXD2-p19−/− GC B cells was associated with decreased expression of CSR-related base excision repair genes that were otherwise predominantly expressed by Il17ra+ cells compared to Ifngr1+ GC B cells in BXD2 mice. Together, these results suggest that although IL-23 is dispensable for GC formation, it is essential for development of the Tfh-IL17 Tfh subpopulation, which drives CSR-related base excision repair genes during the pre-plasmablast GC stage of development.
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| Overall design |
We carried out single cell RNAseq and single-cell V(D)J seq for GC B cells derived from the spleens of BXD2 mice and IL-23-deficient BXD2 (BXD2-p19-/-)mice
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| Contributor(s) |
Hong H, Gao M, Liu S, Hsu H, Mountz JD |
| Citation(s) |
32554431 |
| Submission date |
Feb 25, 2020 |
| Last update date |
Jun 09, 2021 |
| Contact name |
Min Gao |
| E-mail(s) |
mgao@uabmc.edu
|
| Organization name |
University of Alabama at Birmingham
|
| Street address |
1900 University Blvd, THT Building Suite #130G
|
| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35294 |
| Country |
USA |
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| Platforms (2) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA608738 |
| SRA |
SRP250728 |
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