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B 细胞和 T 细胞受体的空间转录组学揭示了淋巴细胞克隆动力学。

Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics.

机构信息

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden.

出版信息

Science. 2023 Dec 8;382(6675):eadf8486. doi: 10.1126/science.adf8486.


DOI:10.1126/science.adf8486
PMID:38060664
Abstract

The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed spatial transcriptomics of variable, diversity, and joining (VDJ) sequences (Spatial VDJ), a method that maps B cell and T cell receptor sequences in human tissue sections. Spatial VDJ captures lymphocyte clones that match canonical B and T cell distributions and amplifies clonal sequences confirmed by orthogonal methods. We found spatial congruency between paired receptor chains, developed a computational framework to predict receptor pairs, and linked the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity and lineage trajectories within their anatomical niche. Thus, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, providing a platform to harness clonal sequences for therapy.

摘要

淋巴细胞克隆在组织内的空间分布对其发育、选择和扩增至关重要。我们开发了可变、多样性和连接(VDJ)序列的空间转录组学(Spatial VDJ),这是一种在人体组织切片中绘制 B 细胞和 T 细胞受体序列的方法。Spatial VDJ 捕获与经典 B 和 T 细胞分布相匹配的淋巴细胞克隆,并扩增通过正交方法确认的克隆序列。我们发现了配对受体链之间的空间一致性,开发了一种计算框架来预测受体对,并将不同 B 细胞克隆的扩增与不同的肿瘤相关基因表达程序联系起来。Spatial VDJ 描绘了 B 细胞克隆多样性及其在解剖学龛位中的谱系轨迹。因此,Spatial VDJ 捕获了淋巴细胞在整个组织中的空间克隆结构,为利用克隆序列进行治疗提供了一个平台。

相似文献

[1]
Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics.

Science. 2023-12-8

[2]
Molecular characterization of Waldenstrom's macroglobulinemia reveals frequent occurrence of two B-cell clones having distinct IgH VDJ sequences.

Clin Cancer Res. 2007-4-1

[3]
Single Cell VDJ Sequencing of Normal and Malignant B and T Cells.

Methods Mol Biol. 2025

[4]
Regulation of antigen receptor gene assembly in lymphocytes.

Immunol Res. 2001

[5]
Frequent occurrence of highly expanded but unrelated B-cell clones in patients with multiple myeloma.

PLoS One. 2013-5-28

[6]
Detection of clonal immunoglobulin and T-cell receptor gene recombination in hematological malignancies: monitoring minimal residual disease.

Cardiovasc Hematol Disord Drug Targets. 2009-6

[7]
[Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].

Veroff Pathol. 1995

[8]
The relevance of VDJ PCR protocols in detecting B-cell clonal expansion in lymphomas and other lymphoproliferative disorders.

Tumori. 1995

[9]
Use of oligonucleotide probes directed against T cell antigen receptor gamma delta variable-(diversity)-joining junctional sequences as a general method for detecting minimal residual disease in acute lymphoblastic leukemias.

J Clin Invest. 1990-12

[10]
Application of the molecular analysis of the T-cell receptor repertoire in the study of immune-mediated hematologic diseases.

Hematology. 2003-6

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