STAT3 but not STAT1 is absolutely required for IL-21–induced differentiation of human naive B cells into ISCs. (A–C) Naive B cells from control donors (A) or STAT3_MUT patients (B) were labeled with CFSE and cultured with CD40L alone or together with IL-21. After 5 d, the percentage of CD38^hiCD27^hi cells was determined. (C) Percentage of CD38^hiCD27^hi cells (mean ± SEM; n = 5) generated per division from control and STAT3_MUT naive B cells stimulated with CD40L/IL-21. (D–G) Naive B cells from healthy controls (D–F: n = 12; G: n = 5), STAT3_MUT patients (D–F: n = 7; G: n = 5), or STAT1_MUT patients (n = 4) were cultured with CD40L alone or together with IL-21 (D–F) or CpG (G). The levels of secreted IgM (D and G), IgG (E), and IgA (F) were determined by ELISA after 12 d. Each symbol represents Ig secretion by naive B cells from an individual normal donor or patient; the horizontal bars represent means. (H–K) Naive B cells from healthy controls or STAT3_MUT or STAT1_MUT patients were cultured with CD40L alone (40L) or together with IL-21 (+IL21) for 5 d. Expression of PAX5 (H), PRDM1 (I), XBP1 (J), and BCL6 (K) was determined by quantitative PCR. The results are means ± SEM (control: n = 12; STAT3_MUT: n = 7; or STAT1_MUT: n = 3 experiments).