Resolving B cell migration from SpatialVDJ sequencing with GIBLE 3612

Abstract Description The spatial dynamics of B cells are crucial during immune response, shaping clonal evolution and affinity maturation. B cell evolution can by studied by reconstructing phylogenetic lineage trees, which represent B cell receptor (BCR) mutations among sampled cells. SpatialVDJ sequencing is a recently developed technique that pairs spatial RNA-sequencing with long-read, spatially resolved BCR data on a 2D slice of tissue. Currently, no methods exist to analyze the movement of B cell lineages across 2D coordinates. We introduce GIBLE (Geographic Inference of B Cell Lineage Evolution), a novel computational framework that reconstructs spatial locations of unobserved, ancestral B cells and quantifies movement across the tissue slice. We used GIBLE to understand B cell maturation in ectopic germinal centers in thymic tissue from patients with myasthenia gravis, an autoimmune disorder in which autoreactive B cells produce antibodies against the neuromuscular junction. GIBLE provides a robust and widely applicable framework for integrating spatial and phylogenetic data to trace B cell evolution during immune responses using SpatialVDJ data. Funding Sources Supported by NIH/NCI 5T32CA134286. Topic Categories Computational and Systems Immunology (COMP)