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Activation of Aicda gene transcription by Pax5 in plasmacytoma cells

  • Immunology in Colorado
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Abstract

Activation-induced deaminase (AID) is an enzyme responsible for somatic hypermutation and immunoglobulin heavy chain class switch recombination. Because AID causes double-stranded breaks in DNA, its expression is highly regulated and is normally restricted to germinal-center B cells. Dysregulated AID expression can lead to cancer as a result of AID-mediated chromosomal translocations. Many transcription factors including paired box protein 5 (Pax5) have been implicated in regulating the expression of Aicda, the gene encoding AID. In this study, we demonstrate that exogenous expression of Pax5 in a murine plasmacytoma cell line, 558LμM, leads to robust activation of endogenous Aicda transcription. Pax5 is known to initiate transcription through both its N-terminal-paired DNA-binding domain and its C-terminal-activation domain. Through mutational analysis, we demonstrate that Pax5 regulates Aicda transcription through its C-terminal-activation domain. Together, our work describes a novel system that will be useful for determining how Pax5 regulates Aicda transcription.

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Acknowledgments

We are indebted to Michael Reth for providing the parent 558LμM and μM.3 subclone and Marian Koshland for the IgA+ CH12 cells. We thank Holly Maier and Julita Ramirez for technical (HM and JR) and editorial (JR) assistance. This work was supported by NIH grants R01 AI054661 and AI081878. CD was in part supported by the Cancer Research Institute Pre-doctoral Emphasis Pathway in Tumor Immunology Fellowship.

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  1. Integrated Department of Immunology, National Jewish Health, Denver, CO, 80206, USA

    Carissa Dege & James Hagman

  2. University of Colorado School of Medicine, Aurora, CO, 80045, USA

    Carissa Dege & James Hagman

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  1. Carissa Dege
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  2. James Hagman
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Correspondence to James Hagman.

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Dege, C., Hagman, J. Activation of Aicda gene transcription by Pax5 in plasmacytoma cells. Immunol Res 55, 155–161 (2013). https://doi.org/10.1007/s12026-012-8357-8

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