# Mechanisms that Regulate Antibody Class Switch Recombination and Somatic Hypermutation

> **NIH NIH R37** · BOSTON CHILDREN'S HOSPITAL · 2024 · $637,200

## Abstract

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.

## Key facts

- **NIH application ID:** 10732811
- **Project number:** 4R37AI077595-16
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Frederick W. Alt
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $637,200
- **Award type:** 4C
- **Project period:** 2008-12-15 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10732811

## Citation

> US National Institutes of Health, RePORTER application 10732811, Mechanisms that Regulate Antibody Class Switch Recombination and Somatic Hypermutation (4R37AI077595-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10732811. Licensed CC0.

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