The splicing regulator PTBP2 is an AID interacting protein and promotes binding of AID to switch region DNA

During immunoglobulin class switch recombination (CSR), activation induced cytidine deaminase (AID) induces DNA double strand breaks into transcribed, repetitive DNA elements called switch sequences. The mechanism that promotes the binding of AID specifically to switch regions remains to be elucidated. We have used a proteomic screen that employs in vivo biotinylation of AID and have identified the splicing regulator polypyrimidine tract binding protein-2 (PTBP2) as an AID interactor. Short hairpin RNA-mediated knock-down of PTBP2 in B cells led to a striking reduction in binding of AID to transcribed switch regions that resulted in marked impairment of CSR. PTBP2 is thus an effector of CSR that promotes binding of AID to switch region DNA.