A CD30 RESPONSIVE ELEMENT IN THE GERMLINE EPSILON-PROMOTER THAT IS DISTINCT FROM AND INHIBITORY TO THE CD40 RESPONSE ELEMENT

Germline epsilon (I epsilon) transcription is requisite for IgE switch recombination. I epsilon transcription is markedly increased by ligat ion of CD40 and/or by IL-4 stimulation. By contrast, we found previous ly that stimulation through CD30 inhibits I epsilon transcription in E BV-transformed B cell lines. To characterize the molecular mechanisms involved in these contradictory events, the promoter elements that are responsible for I epsilon transcriptional regulation were determined using stable CAT reporter gene constructs. The results define a 95 bp CD30 responsive element (CD30RE) located 5' of the previously defined CD40 responsive element (CD40RE) that resides within the same 95 bp fr agment as the IL-4RE and ablates CD40L induced I epsilon promoter acti vity. However, IL-4 overrides the inhibitory effect of CD30L. These re sults define a CD30RE and provide further evidence for the complex reg ulation of I epsilon transcription by various members of the CD40L/TNF alpha. family of molecules. Copyright (C) 1996 Elsevier Science Ltd