Mechanisms that Regulate Antibody Class Switch Recombination and Somatic Hypermutation

Project Summary/Abstract of Research Plans for the Extension Period The first two specific aims of this R37 grant were to test our hypothesis that cohesin-mediated loop extrusion plays a key role in lgH class switch recombination (CSR) and lg variable region exon somatic hypermutation (SHM). A third aim was to test our hypothesis that Peyer's Patch (PP) germinal centers(GCs) expand rare V(D)J clonotypes with high intrinsic SHM levels. For these studies, we developed powerful assays for CSR, SHM and chromatin interactions. We also employed our RAG2-defcient blastocyst complementation approach (RDBC) to generate ES cell-based V(D)J passenger allele and V(D)J-rearranging mouse models for in vivo studies. Despite pandemic challenges, we made substantial progress in the first 3.5 years.