The CD23a and CD23b proximal promoters display different sensitivities to exogenous stimuli in B lymphocytes.
The single human CD23 gene encodes two protein products differing by six or seven amino acids in the extreme N-terminal cytoplasmic domain. The patterns of expression of CD23a and CD23b transcripts differs as a function of cell type and cell stimulation, with expression of CD23a being largely restricted to B cells and CD23b synthesis being inducible in a variety of haematopoietic cells by a range of exogenous stimuli. In this study, short defined sequences of the CD23a and CD23b proximal promoter regions were used to drive expression of exogenous reporter genes in transiently-transfected B cells exposed to a range of cellular stimuli. The CD23a promoter was activated only by IL-4, whereas the CD23b promoter was stimulated not only by IL-4, but also by stimulation with anti-mu, and anti-CD40. Deletion mutant analysis illustrated that of the two putative STAT6 binding sites present in the CD23a proximal promoter, deletion of the first site abrogated IL-4-driven transcriptional activation. Conversely, deletion of both STAT6 binding sites in the CD23b promoter was required before IL-4 sensitivity was lost. When the same CD23b promoter mutants were studied in the context of anti-CD40 and anti-mu stimulation of transfected cells, deletion of the NF-kappaB site abrogated anti-CD40-driven transcriptional activation, but not anti-mu-mediated effects which required additional deletion of putative AP1 sites lying close to the CD23b initiator methionine codon. The data of this report are consistent with the interpretation that the upstream regions of the CD23a and CD23b isoform coding sequences show distinct sensitivities to agents which induce CD23 protein expression at the plasma membrane, and that transcriptional activation by discrete stimuli reflects activation of particular transcriptional regulatory factors.
Ewart
M-A
MA
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
Ozanne
B W
BW
Cushley
W
W
D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D017455:Receptors, IgE / Q000235:genetics*; D017384:Sequence Deletion
D019013:CD40 Antigens; D017455:Receptors, IgE