Evidence for transient requirement of the IgH enhancer

A transcriptional enhancer is thought to play a major role in determining tissue-specific expression of the immunoglobulin heavy chain (IgH) gene (1-3). However in three B-lymphoid cell lines the Ig enhancer has been lost due to a spontaneous deletion, yet heavy chain synthesis persists at a high level (4-6). In the case of the enhancerless delta chain gene (5) we wanted to test whether the IgH enhancer is no longer necessary for maintenance of transcription or whether perhaps a new enhancer was created de novo by the deletion process. To this end we have cloned the relevant portion of the variant IgH gene and transfected it into myeloma and hybridoma cells. We find that the reintroduced gene segment is not expressed unless it is linked again to an enhancer. The results suggest that the IgH enhancer is necessary for the onset of transcription, presumably by organizing the gene into stable transcription complexes, but is dispensable at later stages once the transcription unit is activated.