Isotype switching, AICDA expression, and SHM are unaffected by mutations in STAT3 or STAT1. Naive B cells from (A) normal controls, (B) STAT3_MUT patients, or (C) a STAT1_MUT patient were labeled with CFSE; cultured for 5 d with CD40L alone or together with IL-4, IL-21, or IL-4/IL-21; and analyzed for division and expression of surface IgG. A–C depict contour plots from one experiment. (D) Frequency of IgG⁺ (±SEM) cells in each division (control and STAT3_MUT: n = 7; STAT1_MUT: n = 1). (E) Naive B cells from healthy controls or STAT3_MUT or STAT1_MUT patients were cultured with CD40L alone or with IL-21. After 5 d, expression of AICDA was determined by quantitative PCR. The results are means ± SEM (control: n = 12; STAT3_MUT: n = 7; or STAT1_MUT: n = 3 experiments) and are expressed relative to GAPDH. (F and G) Naive and memory B cells were isolated from three healthy donors and three STAT3_MUT patients. Ig V_H5 genes were cloned and sequenced. (F) The number of mutations detected in each Ig V_H5 gene isolated from normal and STAT3_MUT naive and memory B cells; the horizontal bars represent means. (G) Distribution of mutations in IgV region genes in control and STAT3_MUT memory B cells.