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系统性记忆 B 细胞归档和随机展示塑造了人类一生中的脾脏边缘区。

Systematic memory B cell archiving and random display shape the human splenic marginal zone throughout life.

机构信息

Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.

Department of Haematology, University Hospital Essen, Essen, Germany.

出版信息

J Exp Med. 2021 Apr 5;218(4). doi: 10.1084/jem.20201952.

DOI:10.1084/jem.20201952
PMID:33538775
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7868796/
Abstract

Human memory B cells (MBCs) are generated and diversified in secondary lymphoid tissues throughout the organism. A paired immunoglobulin (Ig)-gene repertoire analysis of peripheral blood (PB) and splenic MBCs from infant, adult, and elderly humans revealed that throughout life, circulating MBCs are comprehensively archived in the spleen. Archive MBC clones are systematically preserved and uncoupled from class-switching. Clonality in the spleen increases steadily, but boosts at midlife, thereby outcompeting small clones. The splenic marginal zone (sMZ) represents a primed MBC compartment, generated from a stochastic exchange within the archive memory pool. This is supported by functional assays, showing that PB and splenic CD21+ MBCs acquire transient CD21high expression upon NOTCH2-stimulation. Our study provides insight that the human MBC system in PB and spleen is composed of three interwoven compartments: the dynamic relationship of circulating, archive, and its subset of primed (sMZ) memory changes with age, thereby contributing to immune aging.

摘要

人体记忆 B 细胞（MBC）在全身的次级淋巴组织中生成和多样化。对婴儿、成人和老年人外周血（PB）和脾 MBC 的配对免疫球蛋白（Ig）基因库分析表明，在整个生命周期中，循环 MBC 都被全面地储存在脾脏中。存档 MBC 克隆被系统地保存下来，并且与类别转换无关。脾克隆的数量不断增加，但在中年时会增加，从而排挤小克隆。脾脏边缘区（sMZ）代表一个预先形成的 MBC 区室，由存档记忆池中随机交换产生。这一观点得到了功能分析的支持，结果表明 PB 和脾 CD21+MBC 在 NOTCH2 刺激下获得短暂的 CD21high 表达。我们的研究提供了一个见解，即 PB 和脾中的人类 MBC 系统由三个相互交织的区室组成：循环、存档及其亚群（sMZ）记忆的动态关系随年龄而变化，从而导致免疫衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/59ae7877d99e/JEM_20201952_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/c9c7afe90d0f/JEM_20201952_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/1e114e962441/JEM_20201952_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/bdb79ed33641/JEM_20201952_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/71050849f8a8/JEM_20201952_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/b14343750a2f/JEM_20201952_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/26476df47575/JEM_20201952_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/2fd08133a729/JEM_20201952_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/170bdfeba76a/JEM_20201952_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/59ae7877d99e/JEM_20201952_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/c9c7afe90d0f/JEM_20201952_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/1e114e962441/JEM_20201952_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/bdb79ed33641/JEM_20201952_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/71050849f8a8/JEM_20201952_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/b14343750a2f/JEM_20201952_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/26476df47575/JEM_20201952_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/2fd08133a729/JEM_20201952_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/170bdfeba76a/JEM_20201952_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b33/7868796/59ae7877d99e/JEM_20201952_FigS3.jpg

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