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转录因子 T-bet 在小鼠和人类中区分具有不同组织分布和抗体特异性的记忆 B 细胞亚群。

The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans.

机构信息

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

出版信息

Immunity. 2020 May 19;52(5):842-855.e6. doi: 10.1016/j.immuni.2020.03.020. Epub 2020 Apr 29.

DOI:10.1016/j.immuni.2020.03.020
PMID:32353250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7242168/
Abstract

B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet and T-bet memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet and T-bet hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet and T-bet MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet MBCs could be subdivided into recirculating T-bet MBCs and spleen-resident T-bet MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.

摘要

B 细胞亚群表达转录因子 T-bet 与体液免疫反应和自身免疫有关。在这里,我们研究了流感特异性免疫反应背景下 T-bet 和 T-bet 记忆 B 细胞(MBC)的解剖分布、克隆关系和功能特性。在小鼠中,T-bet 和 T-bet 血凝素(HA)特异性 B 细胞均在生发中心中出现,获得了记忆 B 细胞标志物,并无限期持续存在。谱系追踪和 IgH 库分析显示 T-bet 和 T-bet MBC 之间几乎没有相互转换,而联体动物显示出不同的组织驻留和再循环特性。T-bet MBC 可进一步分为循环 T-bet MBC 和脾脏驻留 T-bet MBC。人类 MBC 表现出类似的特征。条件基因缺失研究表明,B 细胞中 T-bet 的表达几乎是所有 HA 茎特异性 IgG2c 抗体和流感病毒持久中和滴度所必需的。因此,T-bet 的表达区分了具有截然不同归巢、驻留和功能特性的 MBC 亚群,并介导了体液免疫记忆的不同方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/5d8b89789b84/nihms-1584982-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/38c100125cf6/nihms-1584982-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/636957abe7b4/nihms-1584982-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/544521832015/nihms-1584982-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/5d8b89789b84/nihms-1584982-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/38c100125cf6/nihms-1584982-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/da684079cb03/nihms-1584982-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/636957abe7b4/nihms-1584982-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/544521832015/nihms-1584982-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e8/7242168/5d8b89789b84/nihms-1584982-f0006.jpg

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