In vitro IgE inhibition in B cells by anti-CD23 monoclonal antibodies is functionally dependent on the immunoglobulin Fc domain

CD23, the low affinity receptor for IgE (Fc epsilon RII), is involved in re gulation of IgE synthesis by B-lymphocytes. Five monoclonal antibodies to h uman CD23 were generated from Cynomolgus macaques immunized with purified s oluble CD23 (sCD23). Four of the five primate antibodies blocked the bindin g of IgE complexes to CD23 positive cells and also inhibited the production of IEE in vitro by IL-3 induced human peripheral blood mononuclear cells ( PBMC). The variable domains of several primate antibodies were utilized to construct chimeric macaque/human (PRIMATIZED((R))) monoclonal antibodies. P RIMATIZED((R)) p5E8G1, containing human gamma 1 constant region, inhibited IgE production in vitro as efficiently as the parent primate antibody, but the human gamma 4 constant version, PRIMATIZED((R)) p5E8G4, was not as effe ctive in IgE inhibition. An F(ab')(2) of p5E8G1 did not inhibit IgE product ion but did interfere with IgE inhibition by the intact anti-CD3 antibody i n a dose dependent fashion. The murine monoclonal antibody MHM6 recognizes human CD23 at a different epitope than primate antibody 5E8, and inhibits I gE production by IL-4 induced PBMC. As with the F(ab')(2) of p5E8G1, the F( ab')2 of MHM6 also failed to inhibit IgE production. These data imply that the mechanism by which anti-CD23 antibodies inhibit IgE production requires cross-linking of CD23 to an IgG receptor. These data also imply that neith er bivalent crosslinking of CD23 alone or inhibition of CD23 binding to its natural ligands is sufficient to inhibit IgE production. (C) 2000 Internat ional Society for Immunopharmacology. Published by Elsevier Science Ltd. Al l rights reserved.