IL-23 Promotes a Coordinated B Cell Germinal Center Program for Class-Switch Recombination to IgG2b in BXD2 Mice
| Autor: | PingAr Yang, Jake Y. Chen, Peter D. Burrows, Shanrun Liu, Huixian Hong, John D. Mountz, Hui-Chen Hsu, Min Gao, Qi Wu, Hao Li, Daniel J. Cua |
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| Rok vydání: | 2020 |
| Předmět: |
Immunology
Population Plasma cell Interleukin-23 Article Autoimmune Diseases Transcriptome Interferon-gamma Mice Downregulation and upregulation T-Lymphocyte Subsets medicine Animals Immunology and Allergy Cyclin-Dependent Kinase Inhibitor p19 education B cell Mice Knockout B-Lymphocytes education.field_of_study Chemistry Germinal center Cell Differentiation T helper cell Germinal Center Immunoglobulin Class Switching Molecular biology Mice Inbred C57BL medicine.anatomical_structure Immunoglobulin class switching Immunoglobulin G Th17 Cells |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2000280 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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