Figure 2. Human B cells generated in NOD-scid-IL2Rγ^null mice produce a globally diverse V_H immunoglobulin repertoire that is indistinguishable from normal human peripheral blood B cells.

B lymphocytes were obtained for high-throughput 454 GS-FLX immunoglobulin cDNA gene sequencing. The samples included peripheral blood B cells from two human donors (HuPBC-1, HuPBC-2), naïve B cells (CD19⁺IgD⁺CD27^–) enriched from two humanized mouse spleens (HuMs-1NSpl and HuMs-2NSpl), total splenic B cells from one humanized mouse (HuMs-3TSpl), and newly formed immature B cells (CD24^highCD38⁺IgM⁺IgD^–) pooled from the bone marrow of all three mice (HuMs-ImmB). (A) Engrafted HuMs cells use the full range of IGHV families and display a pattern of utilization similar to control HuPBC samples. Frequencies of IGHV family member use by B cells arising in HuPBC, HuMs, and HuMs-ImmB are comparable between any two samples examined across all IGHV gene families (r_s≥0.89 for all comparisons). One intrafamily statistical difference was discerned, however, for the IGHV4 family (^*** P<0.0001; χ²). (B) Frequencies of IGHD family use are highly similar between HuMs and HuPBC (r_s≥0.86 for all comparisons), although a subtle yet significant trend in elevated IGHD7 family use was discerned among HuMs samples (see text). (C) Frequencies of IGHJ use, like IGHV and IGHD, are statistically similar (r_s≥0.71).