Activation of the mouse Ig germline ε promoter by IL-4 is dependent on AP-1 transcription factors

Induction of germline (GL) epsilon transcripts, an essential step preceding Ig isotype switching to IgE, requires activation of transcription factors by IL-4 and a B cell activator, e.g., CD40 ligand or LPS, We demonstrate that AP-1 (Fos and Jun), induced transiently by CD40 ligand or LPS, binds a DNA element in the mouse GL epsilon promoter. AP-1 synergizes with Stat6 to activate both the intact GL epsilon promoter and a minimal heterologous promoter driven by the AP-I and Stat6 sites of the mouse GL epsilon promoter. By contrast, C/EBP beta, which trans-activates the human GL epsilon promoter, inhibits IL-4 induction of the mouse promoter, probably by attenuating the synergistic interaction between AP-1 and Stat6, Furthermore, AP-1 does not trans-activate the human GL epsilon promoter. Thus, induction of GL epsilon transcripts in mice and humans may be regulated differently. In addition, although mouse GL epsilon transcripts have a half-life of similar to 100 min, the RNA level continues to increase for up to 24 h, and the promoter appears to be active for at least 2 days after B cell activation. Altogether, these data suggest that induction of AP-1 activity, although transient, is required for activation of the mouse GL epsilon promoter by IL-4-induced Stat6.