| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2830937 | Molecular Immunology | 2012 | 10 Pages |
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 CɛmX, 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 CɛmX peptide or its fragments as immunogens for inducing anti-CɛmX antibodies. The results showed that mice immunized subcutaneously with these immunogens produced antibodies that bind to recombinant CɛmX-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-CɛmX peptide immunogens warrant further investigation as a therapeutic modality for modulating IgE in patients with IgE-mediated allergic diseases.
► Membrane-bound IgE (mIgE) is a molecular target for immunological targeting of mIgE-expressing B lymphocytes. ► The CɛmX (also referred to as M1′) segment, located between the CH4 domain and the membrane-anchor peptide of the ɛ chain of mIgE, is a unique antigenic site. ► Immunogens based on CɛmX and hepatitis B core antigen as a carrier protein can elicit antibodies that down-regulate mIgE+ B cells. ► Such immunogens may potentially be vaccine-like therapeutics for IgE-mediated allergic diseases.
