Transcriptional regulation of immunoglobulin gene expression by anti-Ig.

Abstract

When transfected into mouse splenic B cells stimulated with lipopolysaccharide (LPS) the expression of DNA vectors containing the chloramphenicol acetyl transferase gene under the control of a SP6 kappa promoter and the Ig heavy chain intron enhancer could be down-regulated 5- to 10-fold by treatment of the cells with anti-Ig prior to transfection. Exchanging the SP6 kappa promoter by minimal promoters consisting of an octamer or a SP1 motif linked to TATA box did not impair the anti-Ig induced down-regulation while inserting a rabbit beta-globin promoter did. The transcriptional regulation could be observed after replacing the Ig heavy chain intron enhancer with a SV40 enhancer, or duplicated minimal Ig heavy chain enhancers containing or lacking the octamer element. The down-regulation was not dependent on the level of transcriptional stimulation observed. A difference in Oct2 expression could neither be detected at the RNA nor protein level after treatment of LPS stimulated B cells with anti-Ig or phorbol-dibutyrate. Anti-Ig treatment, but not phorbol-di-butyrate treatment, induced increased levels of AP1 and NF kappa B transcription factors. Thus, either differentiation specific transcriptional control of Ig genes is exerted via transcription factors common to several distinct enhancers or via transcriptional adaptor molecules that can interact with several distinct DNA binding proteins.