IL-21 shapes the B cell response in a context-dependent manner Journal Article
| Authors: | Kim, Y.; Manara, F.; Grassmann, S.; Belcheva, K. T.; Reyes, K.; Kim, H.; Downs-Canner, S.; Yewdell, W. T.; Sun, J. C.; Chaudhuri, J. |
| Article Title: | IL-21 shapes the B cell response in a context-dependent manner |
| Abstract: | 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. © 2024 |
| Keywords: | controlled study; nonhuman; flow cytometry; cell proliferation; quality control; animal cell; mouse; stat3 protein; apoptosis; gene expression; interleukin 21; animal experiment; enzyme linked immunosorbent assay; b lymphocyte; somatic hypermutation; saccharomyces cerevisiae; real time polymerase chain reaction; humoral immunity; antibody affinity; biotinylation; immunization; coculture; b cell; hydrodynamics; rna editing; article; class-switching; germinal centers; cp: immunology; il-21 |
| Journal Title: | Cell Reports |
| Volume: | 44 |
| Issue: | 1 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2025-01-28 |
| Start Page: | 115190 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2024.115190 |
| PROVIDER: | scopus |
| PUBMED: | 39792552 |
| PMCID: | PMC11973891 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Jayanta Chaudhuri -- Source: Scopus |
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