Identification and activation mechanism of the interleukin-4-induced nuclear factor binding to the CD23(b) promoter in human B lymphocytes.

CD23 is a B cell activation antigen involved in B cell proliferation and production of IgE, of which two isoforms are known. While CD23(a) is constitutively expressed in B cells, the expression of CD23(b) is specifically induced by interleukin-4 (IL-4) or selected mitogenic stimuli. We have previously shown that CD23(b) is a primary response gene rapidly activated by IL-4 in resting human B cells. We now report the identification of a nuclear factor binding to the IL-4-response element (IL-4RE) in CD23(b) promoter in purified human tonsillar B cells. Activation of this factor, named NF-IL-4/CD23, occurred within 5 min after IL-4 treatment in a cycloheximide-insensitive manner. The activation was sensitive to phosphatases and inhibitors of protein tyrosine kinases, but it was not sensitive to inhibitors of protein kinase C. This behavior, in fact, closely correlates with the IL-4-induced activation mechanism of CD23 gene expression. In transformed B cell line Raji, where the IL-4-induced CD23 mRNA expression was hardly detected, no activation of NF-IL-4/CD23 was noted. The activation was also observed that although a sequence highly homologous to the IL-4RE of the CD23(b) promoter is present in the CD23(a) promoter, the IL-4-induced factor did not bind the sequence. These results strongly suggest that NF-IL-4/CD23 acts as an IL-4 signal transducer leading to CD23(b) gene activation in human B cells. Further characterization of this factor is now in progress, including comparison with STAT6, recently shown to be involved in IL-4 signal transduction and transcriptional activation.