Functional in vitro responses of naive and memory B cells from immunodeficient patients. Naive (A and B) and memory (C and D) B cells were isolated from the peripheral blood of healthy donors or patients with mutations in STAT3, STAT1 (LOF/GOF), IL21R, IL10R, CD40LG (null and hypomorphic [CD40LG*]), NEMO, ICOS, IL12RB1, or IFNGR1, and then cultured with CD40L/IL-21. Secretion of IgM (A and C), IgG and IgA (B and D) was determined after 7 d by Ig heavy chain specific ELISAs. Values represent mean ± SEM. Controls, n = 25; STAT3_DN, n = 6; STAT1_GOF, n = 9; STAT1_LOF, n = 6; IL21R, n = 4; IL10R, n = 2; CD40LG, n = 4; NEMO, n = 5; ICOS, n = 4; IL12R, n = 5; IFNGR1, n = 6. (E and F) total B cells were isolated from healthy donors or patients with mutations in TYK2 (n = 3), and then cultured with CD40L alone or CD40L/IL-21. (E) The proportion of cells acquiring a plasmablast phenotype (CD38^hiCD27^hi) was determined after 5 d by flow cytometry. (F) Ig secretion was determined after 7 d.