Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics
Camilla Engblom, Kim Thrane, Qirong Lin, Alma Andersson, Hosein Toosi, Xinsong Chen, Embla Steiner, Chang Lu, Giulia Mantovani, Michael Hagemann-Jensen, Sami Saarenpää, Mattias Jangard, Julio Sáez-Rodríguez, Jakob Michaëlsson, Johan Hartman, Jens Lagergren, Jeff E. Mold, Joakim Lundeberg, Jonas Frisén
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.