Fig. 5. IGLV3-21^R110 directed CAR T cells spare polyclonal healthy human B cells in vitro and in two humanized mouse models.

a Quantification of polyclonal B cell cytolysis mediated by healthy donor-derived CAR T cells as compared to untransduced cells (UTD) (n = 3 independent experiments). The assay was conducted as those in Fig. 2b–d. Representative images show CAR T cell-mediated cytolysis after 24 h. All conditions indicated have been plotted, negative control conditions overlap. b–e Humanized mouse models to test the specificity of the αR110-CAR T cells. b Workflow of humanized NSG model. c Human PBMCs were injected intravenously (i.v.) in NSG mice followed by i.v. injection of UTD, HD-αR110-CAR T, or HD-αCD19-CAR T cells (for all n = 5) on day 7. The abundance of CD19⁺CD20⁺ B cells relative to all CD45⁺ cells was quantified in the blood on day 8 and 13 using flow cytometry (FC). d Workflow of humanized NFA2 model. e Human PBMCs were intraperitoneally (i.p.) injected into NFA2 mice (n = 4) along with HD-αR110-CAR T or HD-αCD19-CAR T cells. After 16 h mice were sacrificed, peritoneal cells were harvested by peritoneal lavage and quantified using FC. All bar plots represent the indicated mean ± SD. Statistics: one-sided t test. Source data are provided as a Source Data file.