Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements.

The regulation of cell-type specificity of immunoglobulin (lg) mu heavy chain (H) gene expression was examined by introducing various hybrid genes containing lg gene sequences combined with portions of a tissue-nonspecific transcription unit into lymphoid and nonlymphoid cells. Replacing the lymphocyte-specific IgH enhancer with a viral enhancer did not affect tissue specificity of mu Ig gene expression. We identified two new regulatory regions that provide transcriptional tissue specificity. First, the V H promoter region between position -154 and +57 was shown to direct lymphocyte-specific transcription of a bacterial gpt gene, even in the presence of a viral enhancer. Second, mu intragenic sequences, lacking the IgH enhancer, were found to regulate the level of accumulated Ig transcripts in a tissue-specific fashion. These results demonstrate that tissue specificity of Ig gene expression is not solely regulated by the enhancer but that the promoter, and as yet undefined intragenic sequences, contain lymphoid-specific regulatory information.