“…25 Based on our data, including selective blocking of IL-2R on the B cell, we suggest that high concentrations of IL-2 might sensitize the lg B25 ϩ cell to its suppressive function and cause a switch from costimulatory to inhibitory signals. Since the CD25 ϩ B cells directly isolated from PB-a majority of them CD27 ϩ memory B cells (see also Amu et al 33 and T.T., R.K.C.V., V.E., R.S., S.S., A.D.H., unpublished observations, 2008)-did not suppress, whereas the less mature, predominantly CD27-naive B cells from PB did, we suggest that maturation status of the B cell represents another critical parameter in this process. This hypothesis is also supported by an observation during our experiments with B-cell stimulatory CpG-rich oligonucleotides (CpG-ODNs): Although after treatment again only the large B-cell fraction (representing up to 40% of the total B-cell population) exhibited a strong inhibitory effect toward CD4 ϩ T cells, comparable with SAC, the great majority of the B cells (Ͼ 80%) expressed CD25 on the cell surface (T.T., R.C.K.V., V.E., R.S., S.S., A.D.H., and H.-M.L., unpublished observations, 2008).…”