AbstractHuman 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 cellsresulted 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.