E-proteins directly regulate expression of activation-induced deaminase in mature B cells.

Activated mature B cells in which the DNA-binding activity of E-proteins has been disrupted fail to undergo class switch recombination. Here we show that activated B cells overexpressing the antagonist helix-loop-helix protein Id3 do not induce expression of the murine Aicda gene encoding activation-induced deaminase (AID). A highly conserved intronic regulatory element in Aicda binds E-proteins both in vitro and in vivo. The transcriptional activity of this element is regulated by E-proteins. We show that the enforced expression of AID in cells overexpressing Id3 partially restores class switch recombination. Taken together, our observations link helix-loop-helix activity and Aicda gene expression in a common pathway, in which E-protein activity is required for the efficient induction of Aicda transcription.