IL-21–induced expression of CD25 is impaired on STAT3_MUTnaïve B cells. (A-C) Naive B cells from normal donors or patients with loss-of-function mutations in STAT3, STAT1, IL2RG, or IL21R were cultured with CD40L alone (blue) or in combination with IL-21 (red). (A) Expression of IL-2Rα (CD25), IL-2Rβ (CD122), and IL-2Rγ (CD132, γc) on normal and STAT3_MUT B cells or of (B-C) IL-2Rα (CD25) on normal and STAT1_MUT, STAT3_MUT, IL-21R_MUT, or IL2Rγ_MUT B cells was determined after 5 days (or on day 0 for B). The histogram plots in A and B are representative of experiments performed on naïve B cells isolated from 6 normal donors, 6 STAT3-deficient patients, 1 STAT1-deficient patient, 2 IL-2Rγ–deficient patients, and 3 IL-21R–deficient patients. The summary graph in C depicts the mean ± SEM of CD25 expression on cultured B cells from the indicated numbers of patients. (D-E) Naïve B cells from normal donors (blue, n = 7), STAT3-deficient AD-HIES patients (red, n = 6), IL-2Rγ–deficient X-SCID patients (green, n = 2), or IL-21R–deficient patients (black, n = 3) were cultured with CD40L alone (D) or in the presence of IL-21 (E). The mean fluorescence intensity (MFI) of CD25 expression was determined at the indicated times. Results represent mean ± SEM for the indicated number of controls and patients. *P < .005, **P < .001, ***P < .0001.