(A) Humanized mice were generated with CD34+ HSCs transduced with lentiviruses, allowing the expression of different variants of PTPN22 before being injected into the liver of 3-day-old recipient NSG mice. LTR, long terminal repeat. The frequencies of polyreactive (B) and HEp-2–reactive (C) new emigrant B cells from sorted GFP-positive fractions expressing 620W PTPN22, 620R PTPN22, or 263Q PTPN22 were determined and compared with those of GFP-negative new emigrant B cells. Dotted lines show positive control. For each B cell fraction, the frequency of reactive (solid area) and nonreactive (open area) clones is summarized in pie charts, with the total number of clones tested indicated in the center. In summarized reactivity panels on the right, each symbol represents a mouse overexpressing 620W PTPN22 (green dots), 620R PTPN22 (green squares), or 263Q PTPN22 (green triangles). Averages are shown with a bar, and statistically significant differences are indicated.