| Summary: | 博士 === 國立清華大學 === 分子醫學研究所 === 102 === During the development and differentiate of B cell, various isotypes of membrane bound immunoglobulin (mIg) were expressed on the B cell surface. Membrane bound immunoglobulin itself and co-receptors deliver the proliferation and apoptotic signals upon crosslinked by antigens to regulate the B cell development. The heavy chain of mIg differs from that of secreted immunoglobulin in that mIg contains a C-terminal membrane-anchor peptide. Our group previously proposed that the N-terminal extracellular segment of the membrane-anchor peptide of mIg, referred to as the mIg isotype-specific segment (migis), may provide an unique antigenic site for isotype-specific targeting of mIg+ B cells. Here we report the preparation of mouse mAbs specific for human migis-delta and migis-mu. The mAbs bound to human migis containing recombinant proteins in an ELISA, to mIg-expressing transfectants of a CHO cell line and human B cell lines as analyzed by flow cytometry. MC116 cell, which is a mIgD and mIgM expressing human B cell line, could be induced to undergo apoptosis by treatment with those mabs in the presence of a second crosslinking antibody. The production of human IgM by transplanted MC116 cells in NOD-SCID mice could be suppressed by treating with the anti-migis-delta antibody, 20E6. The structure of migis was studied by co-crystallization of anti-migis Fab and migis peptide. These results encourage further investigation of the potential of anti-migis mAbs to control mIg+ B cells, when such a manipulation may alleviate a disease state.
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