气候变化领域集成服务门户(CCPortal): Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth

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DOI	10.1073/PNAS.2016425118
	Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth
	Nakagawa R.; Toboso-Navasaa A.; Schipsb M.; Young G.; Bhaw-Rosun L.; Llorian-Sopena M.; Chakravarty P.; Sesay A.K.; Kassiotis G.; Meyer-Hermann M.; Calado D.P.; Nakagawa R.; Calado D.P.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	Affinity maturation depends on how efficiently germinal centers (GCs) positively select B cells in the light zone (LZ). Positively selected GC B cells recirculate between LZs and dark zones (DZs) and ultimately differentiate into plasmablasts (PBs) and memory B cells (MBCs). Current understanding of the GC reaction presumes that cMyc-dependent positive selection of LZ B cells is a competitive affinity-dependent process; however, this cannot explain the production of GC-derived lower-affinity MBCs or retention of GC B cells with varied affinities. Here, by combining single-cell/bulk RNA sequencing and flow cytometry, we identified and characterized temporally and functionally distinct positively selected cMyc+ GC B cell subpopulations. cMyc+ LZ B cell subpopulations enriched with either higher-or lower-affinity cells diverged soon after permissive positive selection. The former subpopulation contained PB precursors, whereas the latter comprised less proliferative MBC precursors and future DZ entrants. The overall affinity of future DZ entrants was enhanced in the LZ through preferential proliferation of higher-affinity cells. Concurrently, lower-affinity cells were retained in GCs and protected from apoptosis. These findings redefine positive selection as a dynamic process generating three distinct B cell fates and elucidate how positive selection ensures clonal diversity for broad protection. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Affinity maturation; Clonal diversity; GC B cells; Memory B cells; Positive selection
语种	英语
scopus关键词	affinity maturation; apoptosis; article; B lymphocyte subpopulation; cell fate; cell proliferation; flow cytometry; germinal center; human cell; memory cell; plasmablast; RNA sequencing
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181022
作者单位	Immunity and Cancer Laboratory, Francis Crick Institute, London, NW1 1AT, United Kingdom; Helmholtz Centre for Infection Research, Department of Systems Immunology and Braunschweig Integrated Centre for Systems Biology, Braunschweig, 38106, Germany; Retroviral Immunology Laboratory, Francis Crick Institute, London, NW1 1AT, United Kingdom; Advanced Sequencing Laboratory, Francis Crick Institute, London, NW1 1AT, United Kingdom; Bioinformatics and Biostatistics Laboratory, Francis Crick Institute, London, NW1 1AT, United Kingdom; Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, 38106, Germany; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, WC2R 2LS, United Kingdom; Immunity and Cancer Laboratory, Francis Crick Institute, London, NW1 1AT, United Kingdom
推荐引用方式 GB/T 7714	Nakagawa R.,Toboso-Navasaa A.,Schipsb M.,et al. Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth[J],2021,118(2).
APA	Nakagawa R..,Toboso-Navasaa A..,Schipsb M..,Young G..,Bhaw-Rosun L..,...&Calado D.P..(2021).Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Nakagawa R.,et al."Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).