CÉmX peptide-carrying HBcAg virus-like particles induced antibodies that down-regulate mIgE-B lymphocytes.
Mol Immunol
; 52(3-4): 190-9, 2012 Oct.
Article
in En
| MEDLINE
| ID: mdl-22706073
ABSTRACT
Type-I hypersensitivity reactions play a critical role in the pathogenesis of various allergic diseases. The successful development of the anti-IgE antibody, omalizumab, has validated IgE as an effective therapeutic target for the treatment of various IgE-mediated allergic diseases. Two research groups have reported that mAbs specific for certain parts of CÉmX, a domain of 52 aa residues in human membrane-bound IgE (mIgE), can cause the lysis of mIgE-B cells by apoptosis and antibody-dependent cellular cytotoxicity (ADCC). Herein, we explore virus-like particles formed by hepatitis B virus core antigen (HBcAg) that harbors the entire CÉmX peptide or its fragments as immunogens for inducing anti-CÉmX antibodies. The results showed that mice immunized subcutaneously with these immunogens produced antibodies that bind to recombinant CÉmX-containing human IgE.Fc in ELISA and Western blot analyses, and to genetically engineered human mIgE-expressing Ramos B cell line in fluorescence flow cytometric assays. The IgG antibodies purified from the sera of immunized mice were able to cause the apoptosis of mIgE-expressing Ramos cells through a BCR-dependent caspase pathway. Furthermore, the IgG could mediate ADCC in human mIgE-expressing A20 murine B-cell lymphoma. These studies suggest that HBcAg-CÉmX peptide immunogens warrant further investigation as a therapeutic modality for modulating IgE in patients with IgE-mediated allergic diseases.
Full text:
1
Database:
MEDLINE
Main subject:
Immunoglobulin E
/
B-Lymphocytes
/
Antibodies, Anti-Idiotypic
/
Apoptosis
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Vaccines, Virus-Like Particle
/
Hepatitis B Core Antigens
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Mol Immunol
Year:
2012
Type:
Article
Affiliation country:
Taiwan