Role of FcγRIIb and CD23 in the protection from anaphylaxis and clearance of IgE-IgG complexes
To further decipher the protective mechanism, we investigated the role of FcγRIIb and CD23 in the IgE clearance process. For this purpose, we used FcγRIIbKO and CD23KO mice and passively sensitized them to Fel d 1 (Fig. 4A) and Ara R (Fig. 4D) after the passive immunization with the anti-IgE IgG antibodies. While FcγRIIbKO mice were still protected from subsequent challenges with Fel d 1 and Ara R (Figs. 4B and 4E, respectively), CD23KO mice were not (Figs. 4C and 4F). This suggests that protection is primarily mediated by neutralization and is independent of FcγRIIb. Because CD23KO mice were not protected, we hypothesized that IgE-IgG complexes might be eliminated via CD23.
Thus, we investigated the influence of FcγRIIb, CD23, and Fcγ receptors on eliminating IgE-IgG complexes upon anti-IgE IgG administration. Therefore, we immunized Balb/c, CD23KO, FcγRIIbKO, and common Fcγ-chainKO mice (lacking FcεRI, FcγRI, and FcγRIIIa) with IgE-anti-IgE IgG complexes (Fig 4G). and analyzed sera by ELISA 1h after injection. Most complexes were detected in CD23KO mice, followed by Fc-γ−chain KO mice. Significantly fewer IgE-IgG complexes were detected in Balb/c and FcγRIIbKO mice, with no significant difference (Fig 4H, 4I).
These results suggest that CD23 and, to a lesser extent, FcγR mediate the elimination of IgE-IgG complexes, whereas
FcγRIIb alone is not significantly involved in the clearance process.