An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype inhibits basophil degranulation through cross-linking of FcεRI with FcγRIIb

Wigginton, S. J.; Furtado, P. B.; Armour, K. L.; Clark, M. R.; Robins, A.; Emara, M.; Ghaemmaghami, A. M.; Sewell, H. F.; Shakib, F.

Abstract

Background: IgE binds to mast cells and basophils via its high-affinity receptor, FcεRI, and cross-linking of FcεRI-bound IgE molecules by allergen leads to the release of allergic mediators characteristic of type I hypersensitivity reactions. Previous work has shown that cross-linking of FcεRI with FcγRIIb, an ITIM-containing IgG receptor, leads to inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti-idiotype, has broad reactivity with human IgE and as such has the potential to bind simultaneously to FcεRI-bound IgE, via its Fab regions, and the negative regulatory receptor, FcγRIIb, via its Fc region. Objective: To assess the ability of human 2G10 to inhibit anti-IgE and allergen-driven basophil degranulation through cross-linking of FcεRI-bound IgE with FcγRIIb. Methods: 2G10 was assessed for its ability to bind to FcγRIIb on transfected cells and on purified basophils. In the basophil degranulation assay, basophils were purified from peripheral blood of atopic individuals and activated with either anti-IgE or the house dust mite allergen Der p 1, in the presence or absence of human 2G10. Basophil activation was quantified by analysis of CD63 and CD203c expression on the cell surface, and IL-4 expression intracellularly, using flow cytometery. Results: Human 2G10 was able to bind to FcγRIIb on transfected cells and on purified basophils, and induce a dose-dependent inhibition of both anti-IgE and Der p 1-driven degranulation of basophils. Conclusion: The inhibition of basophil degranulation by the human IgG1 anti-idiotype 2G10 highlights the therapeutic potential of IgE-reactive IgG antibodies in restoring basophil integrity through recruitment of the inhibitory receptor FcγRIIb. © 2007 The Authors.

Citation

Wigginton, S. J., Furtado, P. B., Armour, K. L., Clark, M. R., Robins, A., Emara, M., Ghaemmaghami, A. M., Sewell, H. F., & Shakib, F. (2008). An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype inhibits basophil degranulation through cross-linking of FcεRI with FcγRIIb. Clinical and Experimental Allergy, 38(2), 313-319. https://doi.org/10.1111/j.1365-2222.2007.02896.x

• Journal Article Type: Article
• Acceptance Date: Oct 22, 2007
• Online Publication Date: Dec 7, 2007
• Publication Date: Feb 1, 2008
• Deposit Date: Jan 3, 2023
• Journal: Clinical and Experimental Allergy
• Print ISSN: 0954-7894
• Electronic ISSN: 1365-2222
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 38
• Issue: 2
• Pages: 313-319
• DOI: https://doi.org/10.1111/j.1365-2222.2007.02896.x
• Public URL: https://nottingham-repository.worktribe.com/output/3097595
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2007.02896.x