# Class Switch Recombination in B Lymphocytes

> **NIH NIH R37** · ROCKEFELLER UNIVERSITY · 2020 · $423,750

## Abstract

The proposed research continues to focus on the mechanisms that regulate development of the high affinity
antibody responses which are essential to vaccine development. There are several critical aspects to these
responses that are entirely B cell specific. First, clonal expansion which occurs in special microanatomic
structures called germinal centers (GC). Second, diversification of antibody genes by somatic mutation (SHM)
and class switch recombination (CSR), both of which are initiated by activation induced cytidine deaminase
(AID). Although AID prefers antibody genes, it is not entirely lg specific and off target activity is the primary
cause of B cell cancers in humans. The third B cell specific aspect of high affinity antibody development is
selection for clones of B cells that express high affinity receptors. In the first 4 years of the funding period, as
part of the original Aims 1 and 2, we examined the mechanisms by which AID targets lg genes and misstargets
cancer genes in the germinal center. Moreover, we documented the cellular and cell biological regulation of B
cell clonal expansion in the germinal center. We have initiated research on Aim 3 and have made significant
progress in understanding how Rif-1 mediates its effects on CSR by studying its interaction partner ZYMD8
which has an important role in AID targeting.

## Key facts

- **NIH application ID:** 9843087
- **Project number:** 5R37AI037526-26
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Michel C Nussenzweig
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843087

## Citation

> US National Institutes of Health, RePORTER application 9843087, Class Switch Recombination in B Lymphocytes (5R37AI037526-26). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843087. Licensed CC0.

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