气候变化领域集成服务门户(CCPortal): Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice

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DOI	10.1073/pnas.2021570118
	Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice
	da Costa T.A.; Peterson J.N.; Lang J.; Shulman J.; Liang X.; Freed B.M.; Boackle S.A.; Lauzurica P.; Torres R.M.; Pelanda R.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	Central B cell tolerance, the process restricting the development of many newly generated autoreactive B cells, has been intensely investigated in mouse cells while studies in humans have been hampered by the inability to phenotypically distinguish autoreactive and nonautoreactive immature B cell clones and the difficulty in accessing fresh human bone marrow samples. Using a human immune system mouse model in which all human Igκ+ B cells undergo central tolerance, we discovered that human autoreactive immature B cells exhibit a distinctive phenotype that includes lower activation of ERK and differential expression of CD69, CD81, CXCR4, and other glycoproteins. Human B cells exhibiting these characteristics were observed in fresh human bone marrow tissue biopsy specimens, although differences in marker expression were smaller than in the humanized mouse model. Furthermore, the expression of these markers was slightly altered in autoreactive B cells of humanized mice engrafted with some human immune systems genetically predisposed to autoimmunity. Finally, by treating mice and human immune system mice with a pharmacologic antagonist, we show that signaling by CXCR4 is necessary to prevent both human and mouse autoreactive B cell clones from egressing the bone marrow, indicating that CXCR4 functionally contributes to central B cell tolerance. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autoimmunity; B cell tolerance; CXCR4; Hu-mice
语种	英语
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/179830
作者单位	Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, United States; Department of Pathology, University of Colorado, School of Medicine, Children's Hospital of Colorado, Aurora, CO 80045, United States; Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, United States; Department of Medicine, Division of Rheumatology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, United States; Department of Immunology, Centro Nacional de Microbiologia, Majadahonda, Madrid, 28222, Spain; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, United States
推荐引用方式 GB/T 7714	da Costa T.A.,Peterson J.N.,Lang J.,et al. Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice[J],2021,118(16).
APA	da Costa T.A..,Peterson J.N..,Lang J..,Shulman J..,Liang X..,...&Pelanda R..(2021).Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	da Costa T.A.,et al."Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).