Dynamics of local B cell migration during affinity maturation in the human tonsil

Abstract

Affinity maturation enhances B cell binding within germinal centers, where spatial structure preserves sequence diversity by restricting cell movement. While recent studies show that some B cell lineages span multiple germinal centers, the sources, rates and consequences of this spreading process remain unknown. Here, we show that the spatial arrangement of B cells in the human tonsil is driven by local migration during affinity maturation. Through an evolutionary re-analysis of spatial transcriptomics data, we demonstrate that these local migrations follow a clock-like process, in which cells migrate at an average rate of [~]1/50 cell divisions that is consistent across lineages and time. Migrating cells continue to evolve and diversify in their new germinal centers at similar rates, such that the largest lineages in each germinal center often originate from another. These results suggest that affinity maturation operates in a regime of pervasive but intermediate migration, balancing diversity and selection.