Manipulating mIgD-expressing B cells with anti-migis-δ monoclonal antibodies
| Autor: | Hsing-Mao Chu, Hui-Ming Yu, Tse Wen Chang, Chien-Jen Lin, Jiun-Bo Chen, Nien-Yi Chen, Alfur Fu-Hsin Hung, Hwan-You Chang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Immunoglobulin delta-Chains
medicine.drug_class Recombinant Fusion Proteins Molecular Sequence Data Transplantation Heterologous Immunology Population Apoptosis CHO Cells Mice SCID Monoclonal antibody Immunoglobulin D Epitope Cell Line Antibodies Monoclonal Murine-Derived Mice Cricetulus Immune system Antigen Mice Inbred NOD Cricetinae medicine Animals Humans Amino Acid Sequence education Molecular Biology Antibody-dependent cell-mediated cytotoxicity B-Lymphocytes education.field_of_study biology Antibody-Dependent Cell Cytotoxicity Surface Plasmon Resonance Molecular biology Antibodies Anti-Idiotypic Immunoglobulin M biology.protein Epitopes B-Lymphocyte Antibody |
| Zdroj: | Molecular Immunology. 53:187-197 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2012.08.010 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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