title: Manipulating mIgD-expressing B cells with anti-migis-δ monoclonal antibodies.
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.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Nien-Yi
authors.initials: NY
authors.lastname: Chen
authors.forename: Alfur Fu-Hsin
authors.initials: AF
authors.lastname: Hung
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Lin
authors.forename: Jiun-Bo
authors.initials: JB
authors.lastname: Chen
authors.forename: Hsing-Mao
authors.initials: HM
authors.lastname: Chu
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Yu
authors.forename: Hwan-You
authors.initials: HY
authors.lastname: Chang
authors.forename: Tse-Wen
authors.initials: TW
authors.lastname: Chang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D006801:Humans; D007072:Immunoglobulin D / Q000235:genetics / Q000378:metabolism*; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D007138:Immunoglobulin delta-Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D020349:Surface Plasmon Resonance; D014183:Transplantation, Heterologous
chemical_list: D000888:Antibodies, Anti-Idiotypic; D058846:Antibodies, Monoclonal, Murine-Derived; D018985:Epitopes, B-Lymphocyte; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007138:Immunoglobulin delta-Chains; D011993:Recombinant Fusion Proteins