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Mechanisms that Regulate Antibody Class Switch Recombination and Somatic Hypermutation

US · IL NIH grant awarded #nih-5R37AI077595-17

Summary

This research project investigates the mechanisms regulating antibody class switch recombination (CSR) and somatic hypermutation (SHM), and the expansion of V(D)J clonotypes in Peyer's Patch germinal centers.

What they want

The project tests hypotheses regarding the role of cohesin-mediated loop extrusion in lgH class switch recombination (CSR) and lg variable region exon somatic hypermutation (SHM). It also tests the hypothesis that Peyer's Patch germinal centers expand rare V(D)J clonotypes with high intrinsic SHM levels. The work involves developing assays for CSR, SHM, and chromatin interactions, and utilizing a RAG2-deficient 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.
Technical requirements
  • cohesin-mediated loop extrusion
  • lgH class switch recombination (CSR)
  • lg variable region exon somatic hypermutation (SHM)
  • Peyer's Patch (PP) germinal centers (GCs)
  • V(D)J clonotypes
  • assays for CSR, SHM and chromatin interactions
  • RAG2-deficient blastocyst complementation approach (RDBC)
  • ES cell-based V(D)J passenger allele and V(D)J-rearranging mouse models
Mechanisms that Regulate Antibody Class Sw…
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