Poster Presentation Multi-Omics Conference 2024

Stereo-XCR-seq unveils heterogeneity of lymphoid aggregates in perturbed tissues (#114)

Yu Feng 1 , Xiaojuan Zhan 1 , Yi Liu 1 , Yixin Yan 1 , Yanying Guo 1 , Young Li 1
  1. BGI Research, Shenzhen, GUANGDONG, China

T cells and B cells mediate antigen-specific inflammation. Tracing T cell and B cell clonal activity through heritable receptor sequences could provide significant insights on immune surveillance and regulation, while current available tools could not provide clonal information at single cell resolution with spatial distribution simultaneously. To break through this, we developed an ultra-sensitive T/B cell receptor enriching strategy based on stereo-seq. Thus, we yielded a spatially resolved immune repertoire atlas at single cell resolution and observed heterogenic lymphoid aggregates (LAs) with varied clonal activity in perturbed tissues. Specifically, B/plasma cells formed 50-100μm LAs with 10-50 B/plasma cells in kidney cancer concurrent with IgA-nephropathy, while T cells were not primed in the LAs. In lung carcinoma, the LAs could be further categorized into peritumoral tertiary lymphoid structures (TLS), intratumoral TLS and plasma cell aggregates (PCAs). In comparison to the peritumoral TLS, the intratumoral TLS exhibited substantial activities of antigen-binding affinity maturation. The TLS-primed B cells then emigrated from the TLS and formed PCAs in stroma. In PCAs, the plasma cells switched classes to mediate the anti-tumor immune response in the tumor microenvironment. In addition, T cells were primed in the tertiary lymphoid structure in the presence of naïve B cells. Collectively, our study provides an effective approach to profile spatial immune repertoire at single cell resolution with paired αβ and H-L chains, which allow us to make crossing-tissue comparison of T/B cell clonal activities in perturbed tissues.