Activation of the Mouse Ig Germline #epsilon# Promoter by IL-4 Is Dependent on AP-1 Transcription Factors

摘要

Induction of germline (GL) E transcripts, an essential step preceding Ig isotype switching to 19E, requires activation of transcriI tion factors by IL-4 and a B cell activator, e.g., CD40 ligand or LPS. We demonstrate that AP-l (Fos and Jun), induced transient! by CD40 ligand or LPS, binds a DNA element in the mouse GL E promoter. AP-l synergizes with Stat6 to activate both the inta4 GL E promoter and a minimal heterologons promoter driven by the AP-l and Stat6 sites of the mouse GL E promoter. By contras C/EBPfJ, which trans-activates the human GL E promoter, inhibits IL-4 induction of the mouse promoter, probably by attenuatill the synergistic interaction between AP-l and Stat6. Furthermore, AP-l does not trans-activate the human GL E promoter. Thu induction of GL E transcripts in mice and humans may be regulated differently. In addition, although mouse GL E transcripts ha, a half-life of -100 min, the RNA level continues to increase for up to 24 h, and the promoter appears to be active for at least days after B cell activation. Altogether, these data suggest that induction of AP-l activity, although transient, is required fc activation of the mouse GL E promoter by IL-4-induced Stat6.