Low IgG production is a characteristic feature of both the immunodeficiency of recipients of bone marrow transplant (BMT) and the physiologic immunodeficiency of newborns. We tried to determine whether this is due to a B cell defect and whether this can be corrected in vitro by IgG production-promoting cytokines CD40 ligand (CD40L) and interleukin 10 (IL-10). Highly purified circulating B cells from patients at 1 year after transplant, normal neonates and normal adults were cultured with and without anti-mu plus CD40L plus IL-10. Proliferation was measured on day 4 and IgM and IgG production were measured on day 9. Proliferation and IgM production of B cells from patients and from neonates were somewhat low (43-67% of normal). In contrast, IgG production by B cells from patients and from neonates was markedly low (< or = 13% of normal). Decreased IgG production correlated with decreased percentage of B cells negative for membrane IgD (mIgD). We conclude that the low IgG production of normal neonates and patients at 1 year after transplant is, at least in part, caused by a defect of circulating B cells and that this defect cannot be corrected by CD40L and IL-10. Quantitative deficiency of switched mIgD-) B cells probably accounts for this defect.