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Updated: May 7, 2026
09:49
Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
Published on: August 13, 2010
A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination
Bao Q Vuong1, Kayleigh Herrick-Reynolds1, Bharat Vaidyanathan1,2
1Immunology Program, Memorial Sloan-Kettering Cancer Center, Gerstner Sloan-Kettering Graduate School, New York, New York, USA.
Nature Immunology
|October 8, 2013
Summary
DNA breaks trigger phosphorylation of activation-induced cytidine deaminase (AID), enhancing its interaction with APE1 to drive class-switch recombination (CSR). This creates a feedback loop amplifying DNA breaks at immunoglobulin switch regions.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Activation-induced cytidine deaminase (AID) is crucial for immunoglobulin class-switch recombination (CSR).
- AID's phosphorylation at Ser38 is essential for efficient CSR, but the triggers and mechanisms remain unclear.
Purpose of the Study:
- To elucidate the trigger for AID phosphorylation at Ser38.
- To understand the mechanism by which phosphorylated AID facilitates CSR.
Main Methods:
- Investigated the role of DNA breaks in inducing AID phosphorylation.
- Assessed the interaction between AID and the endonuclease APE1.
- Examined the impact of ATM deficiency on AID phosphorylation and APE1 interaction.
Main Results:
- DNA breaks were found to induce AID phosphorylation at Ser38.
- Phosphorylated AID efficiently interacted with APE1, promoting DNA break generation at immunoglobulin switch regions.
- ATM deficiency impaired AID phosphorylation and its interaction with APE1.
Conclusions:
- DNA breaks induce AID phosphorylation, which is critical for its interaction with APE1 and efficient CSR.
- A positive feedback loop involving AID phosphorylation, ATM, and APE1 amplifies DNA breaks at switch regions.
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