1. IL-23 Promotes a Coordinated B Cell Germinal Center Program for Class-Switch Recombination to IgG2b in BXD2 Mice.
- Author
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Hong H, Gao M, Wu Q, Yang P, Liu S, Li H, Burrows PD, Cua D, Chen JY, Hsu HC, and Mountz JD
- Subjects
- Animals, Cell Differentiation, Cyclin-Dependent Kinase Inhibitor p19 genetics, Immunoglobulin Class Switching, Immunoglobulin G genetics, Interferon-gamma metabolism, Interleukin-23 genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Autoimmune Diseases immunology, B-Lymphocytes immunology, Germinal Center immunology, Immunoglobulin G metabolism, Interleukin-23 metabolism, T-Lymphocyte Subsets immunology, Th17 Cells immunology
- Abstract
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-γ. 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., (Copyright © 2020 by The American Association of Immunologists, Inc.)- Published
- 2020
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