NHP B-cell reduction effects of anti-BR3 mAb, BR3-Fc, and anti-CD20 mAb. Comparison of blood B cell numbers from cynomolgus monkeys treated with anti-BR3 mAb (20 mg/kg/week: days 0-29, n = 16; days 29-60, n = 10; terminal d29, n = 6), BR3-Fc (20 mg/kg/week: days 0-29, n = 12; days 29-60, n = 4; terminal d29, n = 8), anti-CD20 (2 × 50 mg/kg: days 0 and 14, n = 4), and vehicle control (same numbers as active agent groups) (A). Anti-BR3 appeared to reduce blood and spleen B cells faster and more profoundly than BR3-Fc but slower and less completely compared with anti-CD20 mAb. Naive lymph node B cells (CD20⁺CD21⁺CD27⁻) were reduced similarly by anti-BR3 and anti-CD20 treatments and less by BR3-Fc. Other lymph node B-cell subsets—memory (CD20⁺CD21⁺CD27⁺), marginal zone (CD20⁺CD21^hiCD27^−/+), germinal center (CD20⁺CD21⁻) cells—were reduced similarly by all treatments (germinal center cells were not assayed in the BR3-Fc-treated experiment) (B). Statistical significance compared with the control treated group is indicated with an asterisk. Because treatment groups were in separate experiments, statistical analysis was always performed against internal vehicle control group. Treatment with anti-BR3 or BR3-Fc result in spleen B-cell reduction measured by immunohistochemistry. B cells, blue (anti-CD20); T cells, orange (anti-CD3) (C). See “Immunofluorescence and immunohistochemistry staining” for image acquisition details.