Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction | |
Li, Xin1,2; Gadzinsky, Adeline1; Gong, Liying1,3; Tong, Haijun1,2; Calderon, Virginie1; Li, Yue1,4; Gu, Hua1,2,3; Kitamura, Daisuke5; Klein, Ulf6; Langdon, Wallace Y.7 | |
刊名 | IMMUNITY
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2018 | |
卷号 | 48期号:3页码:530-+ |
关键词 | Secreting Plasma-cells Class-switch Recombination Memory b Clonal Selection Differentiation Generation Dynamics Proliferation Hypermutation Organization |
ISSN号 | 1074-7613 |
DOI | 10.1016/j.immuni.2018.03.006 |
文献子类 | Article |
英文摘要 | Selective expansion of high-affinity antigen-specific B cells in germinal centers (GCs) is a key event in anti-body affinity maturation. GC B cells with improved affinity can either continue affinity-driven selection or exit the GC to differentiate into plasma cells (PCs) or memory B cells. Here we found that deleting E3 ubiquitin ligases Cbl and Cbl-b (Cbls) in GC B cells resulted in the early exit of high-affinity antigen-specific B cells from the GC reaction and thus impaired clonal expansion. Cbls were highly expressed in GC light zone (LZ) B cells, where they promoted the ubiquitination and degradation of Irf4, a transcription factor facilitating PC fate choice. Strong CD40 and BCR stimulation triggered the Cbl degradation, resulting in increased Irf4 expression and exit from GC affinity selection. Thus, a regulatory cascade that is centered on the Cbl ubiquitin ligases ensures affinity-driven clonal expansion by connecting BCR affinity signals with differentiation programs. |
电子版国际标准刊号 | 1097-4180 |
WOS研究方向 | Immunology |
语种 | 英语 |
WOS记录号 | WOS:000427916900013 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3382] ![]() |
专题 | 生化所2018年发文 |
通讯作者 | Gu, Hua |
作者单位 | 1.Montreal Clin Res Inst, Montreal, PQ H2W 1R7, Canada; 2.Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3T 1J4, Canada; 3.McGill Univ, Div Expt Med, Montreal, PQ H3A 0G4, Canada; 4.McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 0G4, Canada; 5.Tokyo Univ Sci, Res Inst Biomed Sci, Noda, Chiba 1628601, Japan; 6.Univ Leeds, Leeds Inst Canc & Pathol, Sch Med, Leeds LS9 7TF, W Yorkshire, England; 7.Univ Western Australia, Sch Biomed Sci, Crawley, WA 6009, Australia; 8.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China; 9.Feinstein Inst Med Res, Manhasset, NY 11030 USA |
推荐引用方式 GB/T 7714 | Li, Xin,Gadzinsky, Adeline,Gong, Liying,et al. Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction[J]. IMMUNITY,2018,48(3):530-+. |
APA | Li, Xin.,Gadzinsky, Adeline.,Gong, Liying.,Tong, Haijun.,Calderon, Virginie.,...&Zou, Yong-Rui.(2018).Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction.IMMUNITY,48(3),530-+. |
MLA | Li, Xin,et al."Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction".IMMUNITY 48.3(2018):530-+. |
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