SRA

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-?. 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. 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