Anti-BR3 combines 2 mechanisms of action. BALB/c mice (5/group) were treated with the wild-type BAFF-blocking anti-BR3 mAb (CB2), anti-BR3 Fc mutant mAb (CB2-DANA), anti-BR3 nonblocking mAb (PIH11), or BR3-Fc and evaluated for B-cell reduction at days 1 and 6. In blood at day 1, only treatments that had the ability to engage Fcγ receptors and induce ADCC showed B-cell reduction, whereas at day 6, ADCC and survival blockade appear to combine for maximal effects (A). In spleen FO cells, both mechanisms appeared to contribute to B-cell reduction, whereas in MZ, the dominant mechanism appears to be BAFF/BR3-dependent survival blockade. At day 6, the spleen plasma cell compartment was reduced only by ADCC competent molecules (B). Statistical significance compared with the control-treated group is indicated with an asterisk; P values between groups are shown numerically.