IL-23 promotes a coordinated B cell germinal center program for class-switch recombination to IgG2b in BXD2 mice

Academic Article

Abstract

  • Copyright © 2020 by The American Association of Immunologists, Inc. IL-23 promotes autoimmune disease, including Th17 CD4 T cell development and autoantibody production. In this study, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19-/-) mouse leads to a shift of the follicular T helper cell program from follicular T helper (Tfh)-IL-17 to Tfh-IFN-g. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19-/- mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that whereas Ifngr1, Il21r, and Il4r genes exhibited a synchronized expression pattern with Cxcr5 and plasma cell program genes, Il17ra exhibited a synchronized expression pattern with Cxcr4 and GC program genes. Downregulation of Ighg2b in BXD2-p19-/- GC B cells was associated with decreased expression of CSR-related novel base excision repair genes that were otherwise predominantly expressed by Il17ra+ GC B cells in BXD2 mice. Together, these results suggest that although IL-23 is dispensable for GC formation, it is essential to promote a population of Tfh-IL-17 cells. IL-23 acts indirectly on Il17ra+ GC B cells to facilitate CSR-related base excision repair genes during the dark zone phase of GC B cell development.
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    Digital Object Identifier (doi)

    Author List

  • Hong H; Gao M; Wu Q; Yang PA; Liu S; Li H; Burrows PD; Cua D; Chen JY; Hsu HC
  • Start Page

  • 346
  • End Page

  • 358
  • Volume

  • 205
  • Issue

  • 2