Failure of TET2-deficient B cells to undergo class-switch recombination in vivo, generate mature plasma cells, and produce IgG in vitro. (A) Representative flow cytometry dot plots showing almost absent class-switched memory (CD19⁺CD20⁺CD27⁺IgD⁻) B cells and block in expression of surface IgA and IgG in patients, as detected in peripheral blood B cells compared with healthy control and family 2 heterozygous relative. (B) Scheme showing in vitro B-cell differentiation strategy after mimicking a T-cell–dependent immune stimulus. (C) Flow cytometric profile of P3 and healthy control in vitro–differentiating primary B cells, indicating a defect in B-cell maturation and impaired cell survival due to loss of TET2 function. (D) Secreted levels of IgM and IgG detected by enzyme-linked immunosorbent assay during B-cell differentiation showed a failure of class-switch recombination in patient cells. Data are mean ± SD from 2 independent experiments.