Manipulating mIgD-expressing B cells with anti-migis-δ monoclonal antibodies.
Mol Immunol
; 53(3): 187-97, 2013 Mar.
Article
en En
| MEDLINE
| ID: mdl-22944457
ABSTRACT
Surface IgD and IgM doubly positive cells comprise the major population of B cells in the human immune system. The heavy chain of membrane-bound IgD (mδ) differs from that of IgD (δ) in that mδ contains a C-terminal membrane-anchor peptide. Our group previously proposed that the N-terminal extracellular segment of 27 aa residues of the membrane-anchor peptide of mδ, referred to as the mIg isotype-specific-δ (migis-δ) segment, may provide a unique antigenic site for isotype-specific targeting of mIgD(+) B cells. Here we report the preparation of mouse mAbs specific for human migis-δ. The mAbs bound to human migis-δ-containing recombinant proteins in an ELISA and to mIgD-expressing transfectants of a CHO cell line as analyzed by flow cytometry. MAb 20E6, which binds to an epitope toward the N-terminal of human migis-δ, could stain human B cell line MC116, which expressed mIgD and mIgM. MC116 cells could be induced to undergo apoptosis by treatment with 20E6 in the presence of a second crosslinking antibody. Chimeric 20E6 caused antibody-dependent cellular cytotoxicity of MC116 cells in the presence of human PBMCs as the source of effector cells. In cultures of PBMCs, 20E6 down-regulated the population of mIgD(+) B cells. The production of human IgM by transplanted MC116 cells in NOD-SCID (NOD.CB17-Prkdc(scid)/IcrCrlBltw) mice could be suppressed by 20E6. These results encourage further investigation of the potential of anti-migis-δ mAbs to control mIgD(+) B cells, when such a manipulation may alleviate a disease state.
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Bases de datos:
MEDLINE
Asunto principal:
Inmunoglobulina D
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Linfocitos B
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Anticuerpos Antiidiotipos
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Anticuerpos Monoclonales de Origen Murino
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Immunol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Taiwán