3D genome atlas of human tonsil and the role of loop extrusion in B cell somatic hypermutation
B cell maturation within the germinal center tissue microenvironment involves immunoglobulin gene diversification by somatic hypermutation (SHM). How three-dimensional (3D) genome architecture evolves during SHM is not fully understood. We leveraged sequencing-based and image-based 3D genomics and transcriptomics to map single-cell 3D genome organization and gene expression across cell types and states in human tonsils and in B cell lymphoma cell lines. These analyses revealed trajectories of compartment, looping, and nuclear position changes during the B cell immune response and activation of SHM. Targeted protein degradation of RAD21, a component of the cohesion complex, identified its essential role during SHM. Our results provide a [SR2] single-cell 3D genome atlas of human tonsil cells and identify a link between the chromatin loop extrusion machinery and SHM.