We further examined the antigen receptor repertoire diversity in HIS mice, by determining the length of CDR3 hypervariable regions for each Ig-V H gene family. The analysis of CDR3 length distribution of individual HIS mouse splenocytes showed that IgM repertoires are undistinguishable from normal human PBMC IgM repertoires, as measured by the BCR immunoscope analysis ( Figure 1E ). This observation suggests that HIS mice contain a broad variety of naive IgM + B cell clones. The V H -family usage was large and similar to control human PBMC ( Table 1) . The BCR immunoscope analysis was also performed for IgG and IgA repertoires and we observed more restricted repertoires, as expected from B cells undergoing clonal selection and Ig class switch recombination ( Figure S1 ). Immunization of HIS mice with HBV and tetanus vaccines results in the generation of antigen-specific antibody responses