Establishment of a Mouse Anti-ovalbumin IgE Monoclonal Antibody That Induces Fc?RII (CD23)-dependent Activation Without Fc?RI-Dependent Activation.

摘要

IgE mainly activates cells via two receptors, Fc?RI and Fc?RII. Blocking antibodies against and animals genetically targeted for these receptors have been successfully used to distinguish between these two activating pathways. In the present study, we investigated whether our newly established anti-ovalbumin (OVA) monoclonal IgE OE-2 induced Fc?RII-dependent activation, but not Fc?RI-dependent activation in vivo and in vitro, in contrast to the previously established anti-OVA IgE OE-1, which stimulated Fc?RI and Fc?RII. The Fc?RI-mediated degranulation of RBL2H3 cells and passive systemic anaphylaxis in mice were induced by OE-1 but not OE-2. On the other hand, the production of nitric oxide by rat peritoneal macrophages and the primary antibody response in mice against co-injected OVA, which were mediated through Fc?RII, were induced and enhanced by OE-1 and OE-2. Differences in the epitopes recognized by OE-1 and OE-2 may partially explain why OE-1, but not OE-2, triggered Fc?RI-dependent activation. OE-1 bridged Fc?RI through effective aggregation with OVA, whereas OE-2 crosslinked the receptor strongly and only moderately upon the addition of an anti-kappa antibody and polymerized OVA, namely, an OVA-conjugated resin, respectively, resulting in degranulation. Our results offer a novel approach for determining the relative importance of Fc?RI and Fc?RII in various IgE-dependent responses by using OE-1 and OE-2.