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Promoter by IL-4 Is Dependent on AP-1 Transcription Factors1
Department of Molecular Genetics and Microbiology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655
Induction of germline (GL) 
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 promoter.
AP-1 synergizes with Stat6 to activate both the intact GL promoter
and a minimal heterologous promoter driven by the AP-1 and Stat6 sites
of the mouse GL promoter. By contrast, C/EBP
, which
trans-activates the human GL 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 promoter. Thus,
induction of GL transcripts in mice and humans may be regulated
differently. In addition, although mouse GL transcripts have 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 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 promoter by IL-4-induced Stat6.
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