Pax-5 is a key regulator of the B cell-restricted expression of the CD23a isoform.
Human CD23 (the low affinity IgE receptor) is a B cell differentiation marker involved in inflammatory responses. Two isoforms (CD23a and CD23b) are known, which differ only in their cytoplasmic domain. Whereas CD23b expression is specifically induced by IL-4 on B cells and cells of the myeloid lineage, CD23a expression is restricted to B cells. Each isoform is regulated by its own promoter. Pax-5 is a B-cell-restricted transcription factor with an essential role in early and late B cell development. Analyses of the CD23a promoter revealed a Pax-5-binding site, which can compete a high affinity Pax-5-binding site or directly bind Pax-5 protein in electrophoretic mobility shift assays. Introducing mutations into this site abrogates the binding. Expression of Pax-5 in 293 cells resulted in a seven- to tenfold activation of a CD23a core promoter construct. Most importantly, ectopic expression of Pax-5 in the monocytic cell line U-937, which regularly expresses only the CD23b isoform, led to CD23a expression after stimulation with IL-4 and PMA. Our results suggest that Pax-5 is a key regulator of the B-cell-restricted expression of the CD23a isoform.
Medizinische Poliklinik, University of Würzburg, Würzburg, Germany.
Ioana
I
Visan
Martin
M
Goller
Ingolf
I
Berberich
Christian
C
Kneitz
Hans-Peter
HP
Tony
D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008969:Molecular Sequence Data; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D017455:Receptors, IgE / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D020298:U937 Cells
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D020033:Protein Isoforms; D017455:Receptors, IgE; D014157:Transcription Factors; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate