The central B-cell tolerance checkpoint is functional in IPEX patients. (A) Antibodies from new emigrant/transitional B cells from a healthy donor and IPEX patients were tested by ELISA for reactivity against dsDNA, insulin, and lipopolysaccharide (LPS). Dotted lines show ED38-positive control and solid lines show binding for each cloned recombinant antibody. Horizontal lines define cutoff OD₄₀₅ for positive reactivity. For each individual, the frequency of polyreactive (filled area) and nonpolyreactive (open area) clones is summarized in pie charts, with the total number of clones tested indicated in the centers. The frequencies of (B) polyreactive, (C) HEp-2–reactive, and (D) antinuclear new emigrant/transitional B cells in healthy controls and IPEX patients are shown.