The transcription factor Sox2 regulates AID expression in class switched B cells

Immunoglobulin heavy chain (IgH) class switch recombination (CSR) occurs through the deliberate introduction of AID-instigated DNA double strand breaks (DSBs) into the IgH loci. Since DSBs are generally highly toxic, mechanisms that regulate AID expression are of much relevance to both CSR and genomic integrity; however, effectors of such regulatory processes are still poorly understood. Here we show that the transcription factor Sox2 is expressed in activated B cells but almost exclusively in those that have undergone CSR. We demonstrate that enforced expression of Sox2 in splenic B cells severely inhibits AID expression and CSR, while deletion of Sox2 increases the frequency of IgH;c-Myc translocations. These results suggest that Sox2 may regulate AID expression in class-switched B cells to suppress genomic instability associated with CSR.