Work

Suppression of Pathological Allergen-Specific B Cells by Protein-Engineered Molecules in a Mouse Model of Chronic House Dust Mite Allergy

Year: 2024

Type: article

Abstract: Der p1 is one of the major allergens causing house dust mite (HDM) allergy. Pathological Der p1-specific B cells play a key role in allergic inflammation as producers of allergen-specific antibodies. Crosslinking the inhibitory FcγRIIb with the B cell receptor triggers a high-affinity suppressive signal in B cells. Selective elimination of allergen-specific cells could potentially be achieved by administering chimeric molecules that combine, through protein engineering, the FcγRIIb-targeting monoclonal 2.4G2 antibody with the epitope-carrying Dp52–71 peptides from Der p1. We tested this hypothesis, in a chronic mouse model of HDM allergy induced in BalB/c mice, using FACS and ELISA assays, along with histopathological and correlational analyses. Dp52–71chimera treatment of HDM-challenged mice led to a decrease in serum anti-HDM IgG1 antibodies, a reduction in BALF β-hexosaminidase levels, a lowered number of SiglecFhigh CD11clow eosinophils, and an improved lung PAS score. Furthermore, we observed overexpression of FcγRIIb on the surface of CD19 cells in the lungs of HDM-challenged animals, which negatively correlated with the levels of lung alveolar macrophages, neutrophils, and BALF IL-13. Taken together, these results suggest that the use of FcγRIIb overexpression, combined with the expansion of chimeric protein technology to include more epitopes, could improve the outcome of inflammation.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms252413661

Authors: Nikola Ralchev, Silviya Bradyanova, Nikola Kerekov, Andrey Tchorbanov, Nikolina Mihaylova

Institution: Bulgarian Academy of Sciences

Language: English

Topic: Allergic Rhinitis and Sensitization

Subfield: Immunology and Allergy

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,296