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基于生发中心 B 细胞的单细胞分析可为淋巴瘤细胞起源和预后提供信息。

Single-cell analysis of germinal-center B cells informs on lymphoma cell of origin and outcome.

机构信息

Institute for Cancer Genetics, Columbia University, New York, NY.

Department of Pathology and Cell Biology, Columbia University, New York, NY.

出版信息

J Exp Med. 2020 Oct 5;217(10). doi: 10.1084/jem.20200483.


DOI:10.1084/jem.20200483
PMID:32603407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7537389/
Abstract

In response to T cell-dependent antigens, mature B cells are stimulated to form germinal centers (GCs), the sites of B cell affinity maturation and the cell of origin (COO) of most B cell lymphomas. To explore the dynamics of GC B cell development beyond the known dark zone and light zone compartments, we performed single-cell (sc) transcriptomic analysis on human GC B cells and identified multiple functionally linked subpopulations, including the distinct precursors of memory B cells and plasma cells. The gene expression signatures associated with these GC subpopulations were effective in providing a sc-COO for ∼80% of diffuse large B cell lymphomas (DLBCLs) and identified novel prognostic subgroups of DLBCL.

摘要

针对 T 细胞依赖性抗原,成熟 B 细胞受到刺激形成生发中心(GC),这是 B 细胞亲和力成熟的部位,也是大多数 B 细胞淋巴瘤的细胞起源(COO)。为了探索 GC B 细胞发育的动态超出已知的暗区和亮区区室,我们对人类 GC B 细胞进行了单细胞(sc)转录组分析,确定了多个功能相关的亚群,包括记忆 B 细胞和浆细胞的不同前体。与这些 GC 亚群相关的基因表达特征可有效地为大约 80%的弥漫性大 B 细胞淋巴瘤(DLBCL)提供 sc-COO,并确定了 DLBCL 的新的预后亚组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/cf440c7116f0/JEM_20200483_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/75e51727eaab/JEM_20200483_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/eab9eb468962/JEM_20200483_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/a8aedfd59d26/JEM_20200483_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/1dedcfa0a7da/JEM_20200483_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/9cb0b8fe8ac7/JEM_20200483_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/5f1bbfdc76ee/JEM_20200483_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/10f0e3758053/JEM_20200483_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/c7bde76a4d3e/JEM_20200483_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/45c4387ce9cd/JEM_20200483_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/c9248a578704/JEM_20200483_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/e9b641547a63/JEM_20200483_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/fe41fef930a4/JEM_20200483_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/bf58111dddd8/JEM_20200483_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/1481a6018dfd/JEM_20200483_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/cf440c7116f0/JEM_20200483_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/75e51727eaab/JEM_20200483_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/eab9eb468962/JEM_20200483_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/a8aedfd59d26/JEM_20200483_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/1dedcfa0a7da/JEM_20200483_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/9cb0b8fe8ac7/JEM_20200483_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/5f1bbfdc76ee/JEM_20200483_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/10f0e3758053/JEM_20200483_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/c7bde76a4d3e/JEM_20200483_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/45c4387ce9cd/JEM_20200483_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/c9248a578704/JEM_20200483_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/e9b641547a63/JEM_20200483_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/fe41fef930a4/JEM_20200483_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/bf58111dddd8/JEM_20200483_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/1481a6018dfd/JEM_20200483_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d37c/7537389/cf440c7116f0/JEM_20200483_Fig9.jpg

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本文引用的文献

[1]
Gene expression cartography.

Nature. 2019-11-20

[2]
Class-Switch Recombination Occurs Infrequently in Germinal Centers.

Immunity. 2019-7-30

[3]
Protein Amounts of the MYC Transcription Factor Determine Germinal Center B Cell Division Capacity.

Immunity. 2019-7-23

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Cell. 2019-4-18

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Plasma cell differentiation during the germinal center reaction.

Immunol Rev. 2019-3

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Nat Biotechnol. 2018-12-3

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Molecular High-Grade B-Cell Lymphoma: Defining a Poor-Risk Group That Requires Different Approaches to Therapy.

J Clin Oncol. 2018-12-3

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Double-Hit Gene Expression Signature Defines a Distinct Subgroup of Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

J Clin Oncol. 2018-12-3

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Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma.

Nat Commun. 2018-10-1

[10]
MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.

Cancer Cell. 2018-9-10

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