Unique epitopes on C epsilon mX in IgE-B cell receptors are potentially applicable for targeting IgE-committed B cells.
J Immunol
; 184(4): 1748-56, 2010 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-20083663
ABSTRACT
Membrane-bound IgE (mIgE) is part of the IgE-BCR and is essential for generating isotype-specific IgE responses. On mIgE(+) B cells, the membrane-bound epsilon-chain (mepsilon) exists predominantly in the long isoform, mepsilon(L), containing an extra 52 aa CepsilonmX domain between CH4 and the C-terminal membrane-anchoring segment; the short isoform of mepsilon, mepsilon(S), exists in minor proportions. CepsilonmX thus provides an attractive site for immunologic targeting of mIgE(+) B cells. In this study, we show that nine newly prepared CepsilonmX-specific mAbs, as well as the previously reported a20, bound to mIgE.Fc(L)-expressing CHO cells, while only 4B12 and 26H2 bound to mIgE.Fc(L)-expressing B cell line Ramos cells. The mAb 4B12 bound to the N-terminal part, 26H2 the middle part, and all others the C-terminal part of CepsilonmX. Expression of Igalpha and Igbeta on the mIgE.Fc(L)-CHO cells reduces the binding of a20 to CepsilonmX as compared with that of 4B12 and 26H2. The chimeric mAbs c4B12 and c26H2, when cross-linked by secondary antibodies, lysed mIgE.Fc(L)-Ramos cells by apoptosis through a BCR-dependent caspase pathway. Using PBMCs as the source of effector cells, c4B12 and c26H2 demonstrated Ab-dependent cellular cytotoxicity toward mIgE.Fc(L)-Ramos cells in a dose-dependent fashion. In cultures of PBMCs from atopic dermatitis patients, c4B12 and c26H2 inhibited the synthesis of IgE driven by anti-CD40 and IL-4. These results suggest that 4B12 and 26H2 and an immunogen using the peptide segments recognized by these mAbs are potentially useful for targeting mIgE(+) B cells to control IgE production.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inmunoglobulina E
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Receptores de Antígenos de Linfocitos B
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Subgrupos de Linfocitos B
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Cadenas epsilon de Inmunoglobulina
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Marcación de Gen
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Epítopos de Linfocito B
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Taiwán