BCR triggering is required for CpG-induced differentiation of naive but not of memory B cells. Naive (A-B), IgM memory (C-D), and switch memory (E-F) B cells were cultured with CpG 2006 and cytokines in different combinations and in the absence (A,C,E) or in the presence (B,D,F) of anti-Ig. ISCs were measured by isotype-specific ELISPOT on day 6. Data are the mean ± SD of 5 experiments. ▦ indicates IgM; □, IgG; and ▨, IgA.