IL-21 directly induces IL2RA in normal, but not STAT3_MUT, naïve B cells. (A) Naïve B cells were purified from the peripheral blood of normal donors (n = 4) and STAT3-deficient AD-HIES patients (n = 3) and then cultured with CD40L alone (“CD40L”) or together with IL-21 (“+IL-21”). RNA was extracted after 4 days and microarrays performed using Affymetrix Human Gene 1.0 ST Arrays. Genes with marked differences in expression between normal and STAT3-mutant (STAT3_MUT) cells are shown. (B) Naïve B cells from normal donors (n = 10) or patients with loss-of-function mutations in STAT3 (n = 6), STAT1 (n = 4), or IL21R (n = 2) were cultured with CD40L alone (blue) or together with IL-21 (red). RNA was extracted after 5 days and used to determine expression of IL2RA by quantitative polymerase chain reaction. Results show expression levels relative to B cells cultured with CD40L alone. Each symbol represents an individual experiment using cells from a different donor or patient; the horizontal line represents the mean, *P < .05. (C) Chromatin immunoprecipitation (ChIP) was performed on normal LCLs using mouse Ig or anti-STAT3 Ab. Immunoprecipitated chromatin was assessed for the presence of PRDM1 and IL2RA Results are expressed relative to gene expression in the input DNA and represent the mean ± SEM from 3 separate experiments using different LCLs. *P < .05, ***P < .005.