Postdoctoral Research Fellow Geisel Sch. of Med. at Dartmouth Hanover, New Hampshire, United States
Disclosure(s):
Hunter Melton, PhD: No financial relationships to disclose
Introduction/Rationale: The spatial dynamics of B cell affinity maturation during germinal center reactions are critical for effective immune responses. Using B cell receptor (BCR) sequences, computational models can infer the history of mutations within a B cell lineage by building phylogenetic lineage trees. These lineage trees are a powerful way to infer past B cell dynamics during infection, vaccination, and autoimmune diseases. Recently developed spatial sequencing techniques generate BCR sequences across 2D slices of tissue, but no methods exist that use this data to infer the spatial evolution of B cell lineages.
Methods: Here, we introduce GIBLE (Geographic Inference of B Cell Lineage Evolution), a novel Bayesian phylogenetic model that reconstructs spatial locations of unobserved, ancestral B cells, explicitly links mutation rates with physical locations, and quantifies the direction of B cell migration across tissue sections. We applied GIBLE to characterize B cell maturation in the human tonsil.
Results: We find that clonal lineages can seed new germinal centers, leading to parallel evolution of distinct, localized evolutionary clades.
Conclusion: GIBLE provides a robust and broadly applicable framework for integrating spatial and phylogenetic data to trace B cell evolution in space and time during immune responses.
