IgM MBCs encode RBD-specific antibodies, including a neutralizing mAb with improved activity when expressed as IgM vs. IgG. (A and B) Supernatants from cells transfected with plasmids encoding IgM⁺ MBC-derived mAbs as IgG vs. IgM screened by ELISA for anti-IgG (left) or -IgM (right), with untransfected supernatant as a negative control (blue; A); or binding to SARS-CoV-2 spike RBD protein (B). (C) Supernatants’ ability to block RBD from binding to plate-bound human ACE2. BCR clone 204 is highlighted (in red) in B and C. IgG⁺ MBC-derived antibody, 297 IgG, is included as a positive control (in pink) in C. Data are representative of two independent experiments performed in triplicate. (D) BLI data showing binding and dissociation kinetics of BCR clone 204 as purified IgG vs. IgM. (E) SARS-CoV-2 PRNT on Vero cells at the indicated concentrations of 204 IgG vs. IgM or an anti-malaria mAb (negative control; Thouvenel et al., 2021). (F and G) NT₅₀ titers are shown based on mass (F) or molar (G) concentrations. For conditions that did not approach an NT₅₀, an arbitrary NT₅₀ was assigned of 2× the maximum concentration tested (dashed line). The assay was performed in duplicate and repeated at least twice. (H) Epitope mapping of mAb 204 IgG by BLI against well-characterized Fabs/mAbs and the other mAbs in our panel; individual data are provided in Fig. S2, B and D.