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

Engblom C, Thrane K, Lin Q, Andersson A, Toosi H, Chen X, Steiner E, Lu C, Mantovani G, Hagemann-Jensen M, Saarenpää S, Jangard M, Saez-Rodriguez J, Michaëlsson J, Hartman J, Lagergren J, Mold JE, Lundeberg J, Frisén J

Science 382 (6675) eadf8486 [2023-12-08; online 2023-12-08]

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.

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PubMed 38060664

DOI 10.1126/science.adf8486

Crossref 10.1126/science.adf8486

Publications 9.5.0