Class switch recombination (CSR) at the antibody immunoglobulin locus is regulated by germline transcription (GLT)-coupled modifications in the accessibility of the switch region, where CSR takes place. Here we show that histone acetylation of switch regions is linked to CSR but that histone acetylation cannot alone promote CSR or GLT. Activation-induced cytidine deaminase (AID) specifically associates with the CSR target chromatin in a GLT-coupled manner, which may occur potentially by means of physical interaction between AID and the transcription machinery. These data indicate an important role of GLT in the regulation of chromatin accessibility, strongly suggesting that the target of AID is chromatin DNA. Our results give insights on the role of AID and the regulatory mechanism of CSR.

Pax5 activity is enhanced in activated B cells and is essential for class switch recombination (CSR). We show that inhibitor of differentiation (Id)2 suppresses CSR by repressing the gene expression of activation-induced cytidine deaminase (AID), which has been shown to be indispensable for CSR. Furthermore, a putative regulatory region of AID contains E2A- and Pax5-binding sites, and the latter site is indispensable for AID gene expression. Moreover, the DNA-binding activity of Pax5 is decreased in Id2-overexpressing B cells and enhanced in Id2−/− B cells. The kinetics of Pax5, but not E2A, occupancy to AID locus is the same as AID expression in primary B cells. Finally, enforced expression of Pax5 induces AID transcription in pro–B cell lines. Our results provide evidence that the balance between Pax5 and Id2 activities has a key role in AID gene expression.