Targeted suppression of Dpt-specific B cells in humanized Rag2- γc- mouse model of HDM allergy.
Scand J Immunol
; 97(2): e13241, 2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36519562
ABSTRACT
Der p 1 is one of the major allergenic molecules of Dermatophagoides pteronyssinus, causing house dust mite (HDM) allergy. The pathological B cells produce allergen-specific IgE antibodies that mediate the hypersensitivity reaction, therefore the selective elimination of these B cells is a legitimate therapeutic goal in allergy. Chimeric molecule Dp51-72 able to cross-link B cell inhibitory complement receptor type 1 and BCR on Der p 1-specific B cells was constructed. The signalling capabilities of this molecule have been tested on human B cells. A humanized mouse model of HDM allergy has been used to test the in vivo effects of the chimeric molecule administration. Administering the chimeric molecule to immunodeficient Rag2- γc- mice transferred with PBMCs from allergic patients resulted in reduction of allergen-specific IgE antibodies in the sera, and reduced infiltration of immune cells in lung histology preparations. Reduced numbers of human CD45+ and CD4+ cells in the lungs as well as inhibition of mast cell degranulation were also observed. The treatment with Dp51-72 chimera significantly decreased the local levels of anti-Dpt IgE antibodies in the bronchoalveolar lavage fluid (BALF). The binding of the chimeric molecule to tonsillar B cells triggers the tyrosine phosphorylation of 30-32 kDa protein, which is most likely involved in the inhibitory process. Administration of constructed chimeric molecules to humanized mice with developed inflammation resulted in specific suppression of disease-associated IgE antibody-producing cells and preserved lung histology. This effective approach could be further developed into a therapeutic agent for treatment of patients with HDM allergy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos B
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Alergia a Ácaros
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Hipersensibilidade
Limite:
Animals
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Humans
Idioma:
En
Revista:
Scand J Immunol
Ano de publicação:
2023
Tipo de documento:
Article