Proof-of-concept experiment of antibody feedback with mouse immunization model. (A) Schematic of experimental design for B and C. (B) Serum anti–RBD-W and anti–RBD-O IgG titers collected 21 d after immunization of wild-type mice with RBD-W. (C) Left: Flow cytometry analysis of day 13 or day 35 splenocytes of mice immunized with RBD-W on day 0 and injected with serum on day 5. Right: Total cell number of RBD-W⁺ IgG⁺ GC or memory B cells and summary of the frequency of RBD-O⁺ cells among RBD-W⁺ IgG⁺ GC or memory B cells. (D) Schematic of the experimental design for E and F. (E) Serum anti–RBD-W IgG titers collected on day 21 after immunization and DTX administration from BM chimeras reconstituted with mixed BM cells from μMT (80%) and CD138-DTR (20%) mice. Control groups were reconstituted with μMT (80%) and wild-type (20%) BM cells. (F) Left: Flow cytometry analysis of day 25 or day 35 splenocytes of BM chimeras. Right: Total cell number of RBD-W⁺ switched GC B cells or plasmablasts and summary of the frequency of RBD-O⁺ cells among RBD-W⁺–switched GC B cells or plasmablasts. Red bars represent means. Representative of two independent experiments. *, P < 0.05; **, P < 0.01; ****, P < 0.0001 by unpaired two-tailed Student’s t test.