Pax-5 is a key regulator of the B cell-restricted expression of the CD23a isoform
Autor: | Martin Goller, Hans-Peter Tony, Ioana Visan, Ingolf Berberich, Christian Kneitz |
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Rok vydání: | 2003 |
Předmět: |
Gene isoform
Immunology Molecular Sequence Data Biology medicine Immunology and Allergy Humans Protein Isoforms Promoter Regions Genetic Transcription factor B cell Regulation of gene expression B-Lymphocytes Binding Sites Base Sequence Receptors IgE HEK 293 cells PAX5 Transcription Factor Promoter U937 Cells Molecular biology DNA-Binding Proteins medicine.anatomical_structure Gene Expression Regulation Cell culture Tetradecanoylphorbol Acetate Ectopic expression Interleukin-4 Transcription Factors |
Zdroj: | European journal of immunology. 33(5) |
ISSN: | 0014-2980 |
Popis: | 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. |
Databáze: | OpenAIRE |
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