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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:p>The spatial organization of adaptive immune cells within lymph nodes is critical for understanding immune responses during infection and disease. Here, we introduce AIR-SPACE, an integrative approach that combines high-resolution spatial transcriptomics with paired, high-fidelity long-read sequencing of T and B cell receptors. This method enables the simultaneous analysis of cellular transcriptomes and adaptive immune receptor (AIR) repertoires within their native spatial context. We applied AIR-SPACE to mouse popliteal lymph nodes at five distinct time points after Vaccinia virus footpad infection and constructed a comprehensive map of the developing adaptive immune response. Our analysis revealed heterogeneous activation niches, characterized by Interferon-gamma (IFN-\u03b3) production, during the early stages of infection. At later stages, we delineated subanatomical structures within the germinal center (GC) and observed evidence that antibody-producing plasma cells differentiate and exit the GC through the dark zone. Furthermore, by combining clonotype data with spatial lineage tracing, we demonstrate that B cell clones are shared among multiple GCs within the same lymph node, reinforcing the concept of a dynamic, interconnected network of GCs. Overall, our study demonstrates how AIR-SPACE can be used to gain insight into the spatial dynamics of infection responses within lymphoid organs.<\/jats:p>","DOI":"10.1073\/pnas.2504742123","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T20:01:11Z","timestamp":1769457671000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":10,"title":["A temporal and spatial atlas of adaptive immune responses in the lymph node following viral infection"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-0161","authenticated-orcid":false,"given":"Shaowen","family":"Jiang","sequence":"first","affiliation":[{"name":"Meinig School of Biomedical Engineering, Cornell University","place":["Ithaca"]},{"name":"Department of Computational Biology, Cornell 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Dobin STARsolo: Accurate fast and versatile mapping\/quantification of single-cell and single-nucleus RNA-seq data. bioXiv [Preprint] (2021). https:\/\/doi.org\/10.1101\/2021.05.05.442755. Accessed 21 October 2025.","DOI":"10.1101\/2021.05.05.442755"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"e_1_3_4_61_2","unstructured":"S. Jiang Spatiotemporal dynamics of the lymph adaptive immune repertoire in response to viral infection. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE286452. Deposited 11 January 2025."},{"key":"e_1_3_4_62_2","unstructured":"S. Jiang AIR-SPACE code. GitHub. https:\/\/github.com\/ShaowenJCornell\/AIR-SPACE. 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