A temporal and spatial atlas of adaptive immune responses in the lymph node following viral infection
- Shaowen Jiang
- Jahanara Freedman
- Madhav Mantri
- Viviana Maymi
- Scott A. Leddon
- Peter Schweitzer
- Subash Bhandari
- Chase Holdener
- Ioannis Ntekas
- Christopher Vollmers
- Andrew I. Flyak
- Deborah J. Fowell
- Brian D. Rudd
- Iwijn De Vlaminck
2026-01-26
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-γ) 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.