IL-21 shapes the B cell response in a context-dependent manner
Summary: The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015419 |
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| author | Youngjun Kim Francesca Manara Simon Grassmann Kalina T. Belcheva Kanelly Reyes Hyunu Kim Stephanie Downs-Canner William T. Yewdell Joseph C. Sun Jayanta Chaudhuri |
| author_facet | Youngjun Kim Francesca Manara Simon Grassmann Kalina T. Belcheva Kanelly Reyes Hyunu Kim Stephanie Downs-Canner William T. Yewdell Joseph C. Sun Jayanta Chaudhuri |
| author_sort | Youngjun Kim |
| collection | DOAJ |
| description | Summary: The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1+ B cells. In vivo, B-cell-specific Il21r deletion impaired IgG1 responses post-immunization and disrupted progression from pre-GC to GC states. Although Il21r deficiency did not affect the proportion of IgG1+ cells among GC B cells, it greatly diminished the proportion of IgG1+ cells among the plasmablast/plasma cell population. Collectively, our findings suggest that IL-21 serves as a critical regulator of B cell fates, influencing B cell apoptosis and proliferation in a context-dependent manner. |
| format | Article |
| id | doaj-art-ec6f7cada267470e9fcd9ed50d33e56f |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-ec6f7cada267470e9fcd9ed50d33e56f2025-01-11T06:41:13ZengElsevierCell Reports2211-12472025-01-01441115190IL-21 shapes the B cell response in a context-dependent mannerYoungjun Kim0Francesca Manara1Simon Grassmann2Kalina T. Belcheva3Kanelly Reyes4Hyunu Kim5Stephanie Downs-Canner6William T. Yewdell7Joseph C. Sun8Jayanta Chaudhuri9Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Corresponding authorDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; BCMB Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, New York, NY 10065, USADepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Immunology Discovery, Genentech Inc, South San Francisco, CA 94080, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, New York, NY 10065, USA; Corresponding authorSummary: The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1+ B cells. In vivo, B-cell-specific Il21r deletion impaired IgG1 responses post-immunization and disrupted progression from pre-GC to GC states. Although Il21r deficiency did not affect the proportion of IgG1+ cells among GC B cells, it greatly diminished the proportion of IgG1+ cells among the plasmablast/plasma cell population. Collectively, our findings suggest that IL-21 serves as a critical regulator of B cell fates, influencing B cell apoptosis and proliferation in a context-dependent manner.http://www.sciencedirect.com/science/article/pii/S2211124724015419CP: Immunology |
| spellingShingle | Youngjun Kim Francesca Manara Simon Grassmann Kalina T. Belcheva Kanelly Reyes Hyunu Kim Stephanie Downs-Canner William T. Yewdell Joseph C. Sun Jayanta Chaudhuri IL-21 shapes the B cell response in a context-dependent manner Cell Reports CP: Immunology |
| title | IL-21 shapes the B cell response in a context-dependent manner |
| title_full | IL-21 shapes the B cell response in a context-dependent manner |
| title_fullStr | IL-21 shapes the B cell response in a context-dependent manner |
| title_full_unstemmed | IL-21 shapes the B cell response in a context-dependent manner |
| title_short | IL-21 shapes the B cell response in a context-dependent manner |
| title_sort | il 21 shapes the b cell response in a context dependent manner |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015419 |
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