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Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
Published on: August 13, 2010
PTIP promotes chromatin changes critical for immunoglobulin class switch recombination
Jeremy A Daniel1, Margarida Almeida Santos, Zhibin Wang
1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Science (New York, N.Y.)
|July 31, 2010
Summary
PTIP, a protein crucial for DNA repair, regulates immunoglobulin class switching by controlling DNA accessibility. Its absence impairs antibody function and genome stability.
Area of Science:
- Immunology
- Molecular Biology
- Epigenetics
Background:
- Programmed genetic rearrangements in lymphocytes depend on transcription for DNA double-strand break (DSB) formation.
- Antigen receptor gene transcription is vital for DNA recombination and repair processes.
Purpose of the Study:
- To investigate the role of PTIP in the MLL3-MLL4 complex in immunoglobulin heavy-chain (Igh) locus regulation.
- To determine PTIP's function in immunoglobulin class switching and genome stability.
Main Methods:
- Analysis of activated B cells deficient in PTIP.
- Assessment of histone 3 lysine 4 trimethylation (H3K4me3) and transcription initiation at the Igh locus.
- Evaluation of PTIP's role in DSB repair and class switch recombination (CSR).
Main Results:
- PTIP deficiency in activated B cells led to reduced H3K4me3 and impaired transcription initiation at the Igh locus.
- Loss of PTIP resulted in defective immunoglobulin class switching.
- PTIP accumulation at DSBs was found to be essential for CSR and genome stability, independent of Igh switch transcription.
Conclusions:
- PTIP facilitates crucial chromatin modifications that regulate Igh locus accessibility for CSR.
- The MLL3-MLL4 complex, via PTIP, plays a nonredundant role in modulating antibody effector functions.
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