Antagonistic properties of CB1 variants in vitro and in vivo. (A) CB2-IgG and CB3s-IgG inhibit BAFF/anti-IgM costimulated primary human B-cell proliferation as described in “Materials and methods.” (B) Human B cells were treated with anti-IgM and increasing concentrations of control, CB2-IgG, CB3s-IgG, or a hybridoma-derived agonistic anti-BR3 antibody control. Only the agonistic antibody showed dose-dependent B-cell proliferation. (C) Blood and (D) spleen B-cell numbers in groups of 5 Balb/C mice 6 days after treating with control, BR3-Fc, and CB2-IgG* (IgG with ablated Fc-mediated effector function). Error bars indicate standard error of the mean (SEM) of 5 mice per group.