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

• 成果类型: Article
• 署名作者: Engblom, Camilla; Thrane, Kim; Lin, Qirong; Andersson, Alma; Toosi, Hosein; Chen, Xinsong; Steiner, Embla; Lu, Chang; Mantovani, Giulia; Hagemann-Jensen, Michael; Saarenpaa, Sami; Jangard, Mattias; Saez-Rodriguez, Julio; Michaelsson, Jakob; Hartman, Johan; Lagergren, Jens; Mold, Jeff E.; Lundeberg, Joakim; Frisen, Jonas
• 署名单位: Karolinska Institutet; Royal Institute of Technology; SciLifeLab; SciLifeLab; Royal Institute of Technology; Karolinska Institutet; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Sophiahemmet University; Karolinska Institutet; Karolinska Institutet; Karolinska University Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9227
• DOI: 10.1126/science.adf8486
• 发表日期: 2023-12-08
• 页码: 1137-+
• 关键词: germinal-centers; diversity; toolkit

摘要

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.