We have generated HIS mice by transplanting human HSC into alymphoid BALB/c Rag2 2/2 IL-2Rcc 2/2 newborn mice ( Figure 1A ). As reported previously, multilineage human hematopoietic reconstitution is observed in HIS mice, which demonstrate human thymopoiesis, B cell differentiation, NK cell and plasmacytoid dendritic cell development, and myelopoiesis [10, 13, 14, 15, 16] . Human immune cells accumulate in lymphoid tissues, and several B cell subsets are observed in HIS mice ( Figure 1B) . We analyzed the human B cell repertoire present in naive HIS mice by using B cell receptor (BCR) immunoscope analysis based on quantitative PCR of Ig variable (V H ) and constant (C H ) region gene segments [17] . Due to the lack of human spleen samples, the cells isolated from HIS mouse spleens, which contained sufficient numbers of human B cells to perform the immunoscope analysis, were compared to control human peripheral blood mononuclear cells (PBMC) samples, which were considered acceptable for the purpose of the performed comparison. We observed that IgM-expressing B cells as well as Ig isotype-switched B cells are found in naive HIS mice ( Figure 1C) . The vast majority of B cells of HIS mice expressed an IgM (97.961.0%), whereas IgG (1.861.0%) and IgA (0.0760.04%) expressing B cells represented minor populations. Only the frequency of IgA-expressing B cells was found significantly higher in control human PBMC samples (p,0.0001). At 10-14 weeks post-transplantation (i.e. in steady state conditions), the human Ig concentrations in the blood were 12268 mg/ml (IgM) and 143612 mg/ml (IgG) ( Figure 1D ), as previously reported [8, 16] . In comparison, the normal range for Ig concentration in healthy humans is 400-3100 mg IgM/ml and 7200-14700 mg IgG/ml. In brief, despite a low frequency of IgG-expressing cells, both human IgM and IgG accumulated in the plasma of ,3 month-old HIS mice to levels representing around 10% and 1% of adult human IgM and IgG concentrations, respectively.