IL-21 shapes the B cell response in a context-dependent manner.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY
Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-09 DOI:10.1016/j.celrep.2024.115190
Youngjun Kim, Francesca Manara, Simon Grassmann, Kalina T Belcheva, Kanelly Reyes, Hyunu Kim, Stephanie Downs-Canner, William T Yewdell, Joseph C Sun, Jayanta Chaudhuri
{"title":"IL-21 shapes the B cell response in a context-dependent manner.","authors":"Youngjun Kim, Francesca Manara, Simon Grassmann, Kalina T Belcheva, Kanelly Reyes, Hyunu Kim, Stephanie Downs-Canner, William T Yewdell, Joseph C Sun, Jayanta Chaudhuri","doi":"10.1016/j.celrep.2024.115190","DOIUrl":null,"url":null,"abstract":"<p><p>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<sup>+</sup> 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<sup>+</sup> cells among GC B cells, it greatly diminished the proportion of IgG1<sup>+</sup> 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.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115190"},"PeriodicalIF":7.5000,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2024.115190","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

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.

IL-21以上下文依赖的方式塑造B细胞反应。
t细胞来源的细胞因子IL-21对生发中心(GC)应答至关重要,但其在B细胞功能中的确切作用仍不清楚。利用IL-21受体(Il21r)条件敲除小鼠和离体培养系统,我们证明IL-21对B细胞具有双重作用。虽然IL-21在初始B细胞中以stat3依赖的方式诱导凋亡,但它促进了预激活B细胞的强劲增殖,特别是IgG1+ B细胞。在体内,b细胞特异性Il21r缺失会破坏免疫后的IgG1反应,并破坏从GC前到GC状态的进展。虽然Il21r缺乏不影响IgG1+细胞在GC B细胞中的比例,但它大大降低了IgG1+细胞在浆母细胞/浆细胞群体中的比例。总之,我们的研究结果表明,IL-21作为B细胞命运的关键调节剂,以上下文依赖的方式影响B细胞凋亡和增殖。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信