Spatial Mapping of the Adaptive Immune Receptor Repertoire in Lymph Nodes During Viral Infection 2278

Abstract Description The spatial organization of adaptive immune cells within lymph nodes is essential for understanding immune responses during infection and disease. Here, we sought to investigate the spatial and temporal changes to the adaptive immune receptor repertoire (AIRR) in the draining lymph node after footpad infection with Vaccinia virus in mice. We developed a novel method that combines high-resolution spatial transcriptomics (Slide-seq) with high-fidelity long-read adaptive immune receptor sequencing from tissue sections. This integration enables simultaneous analysis of whole transcriptomes and the AIRR in their spatial context. Applying our method to the model, we demonstrated its capability to map the spatial distribution and capture temporal dynamics of the AIRR at 3, 7, 10, 14, and 21 days post-infection. Our approach revealed heterogenous niches of activation from Interferon-gamma (IFN-γ) during early stages of infection. We also observed sub-anatomical structures within the germinal center (GC), providing evidence that antibody-producing plasma cells differentiate and exit the GC from the dark zone. Additionally, we traced the spatial lineage trajectory of B cell clones and found evidence to suggest that their maturation occurs across multiple GCs. Thus, our methodology offers valuable insights into the spatial dynamics of immune responses, presenting a powerful tool for studying the immune system and disease pathogenesis. Topic Categories Technological Innovations in Immunology (TECH)