YY1 Controls Immunoglobulin Class Switch Recombination and Nuclear Activation-Induced Deaminase Levels

Abstract

Activation-induced deaminase (AID) is an enzyme required for class switch recombination (CSR) and somatic hypermutation (SHM), processes that ensure antibody maturation and expression of different immunoglobulin isotypes. AID function is tightly regulated by tissue- and stage-specific expression, nuclear localization, and protein stability. Transcription factor YY1 is crucial for early B cell development, but its function at late B cell stages is unknown. Here, we show that YY1 conditional knockout in activated splenic B cells interferes with CSR. Knockout of YY1 did not affect B cell proliferation, transcription of the AID and IgM genes, or levels of various switch region germ line transcripts. However, we show that YY1 physically interacts with AID and controls the accumulation of nuclear AID, at least in part, by increasing nuclear AID stability. We show for the first time that YY1 plays a novel role in CSR and controls nuclear AID protein levels.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.05989-11.

ACKNOWLEDGMENTS

We thank Hua Ding from the Protein Core at Children's Hospital of Philadelphia for purification of TAT-CRE. We thank Fred Alt for the AID cDNA, T. Honjo for CH12F3 cells, Matthew Thomas and Dave Allman for advice on CSR assays, and Bruce Freedman and Craig Bassing for helpful discussions and advice.

This work was supported by NIH grants RO1 AI079002 and GM082841.