Nat Commun | 冯驭/曾泽贤/周京颖开发空间免疫组库Stereo-XCR-seq技术平台，实现原位单细胞分辨率T/B细胞受体全景解析

TL;DR - A Nature Communications paper (Aug 3, 2026) from Feng Yu (SIAT/BGI Research), Zeng Zexian (PKU), and Zhou Jingying (CUHK) introduces Stereo-XCR-seq, a spatial immune-repertoire sequencing platform that captures paired TCR/BCR sequences at true single-cell resolution in situ. It matters because it lets researchers map clonal expansion and antigen-specific lymphocyte responses directly onto tissue architecture, with direct hooks into TCR-T therapy and antibody discovery.

• sscirPCR chemistry: double-stranded cDNA is heat-denatured, snap-annealed to single strands, and circularized via oligo ligation; constant-region primers then amplify without V-gene primer/probe bias, placing the spatial barcode and V(D)J at opposite ends so short-read sequencing recovers both. Solves the >1000 bp barcode–V(D)J distance and <0.01% transcript abundance problems; ~1000+ clonotypes per section.
• True single-cell resolution: combining ssDNA staining with the CellBin2 segmentation algorithm on BGI's Stereo-seq platform beats the 100 μm resolution of Spatial VDJ / SPTCR-seq, which the authors show distorts clone-size quantification and chain pairing.
• Biology finding: across 11 lung adenocarcinoma samples containing only immature TLS (no CD23⁺ secondary follicles), B cells emigrate and form distal plasma cell zones (PCZ) acting as ectopic germinal-center-like niches — IgM⁺ PCZ shows SHM with high AICDA, IgG⁺ PCZ enriches tumor-reactive T clones (TNF, TCF7, FASLG), with CD40LG–CD40 driving CSR and terminal differentiation, mimicking GC light/dark zones.
• Breadth and translation: works on both fresh-frozen and FFPE retrospective clinical samples; validated in colorectal, gastric, bladder, and renal cancers plus autoimmune hepatitis and rheumatoid arthritis. Paired TCRα/β recovery feeds TCR-T receptor design; in situ SHM/CSR tracking supports antibody screening.