title: B-cell maturation antigen is modified by a single N-glycan chain that modulates ligand binding and surface retention.
abstract: Glycosylation, an important posttranslational modification process, can modulate the structure and function of proteins, but its effect on the properties of plasma cells is largely unknown. In this study, we identified a panel of glycoproteins by click reaction with alkynyl sugar analogs in plasma cells coupled with mass spectrometry analysis. The B-cell maturation antigen (BCMA), an essential membrane protein for maintaining the survival of plasma cells, was identified as a glycoprotein exhibiting complex-type N-glycans at a single N-glycosylation site, asparagine 42. We then investigated the effect of N-glycosylation on the function of BCMA and found that the dexamethasone-induced apoptosis in malignant plasma cells can be rescued by treatment with BCMA ligands, such as a proliferation-inducing ligand (APRIL) and B-cell-activating factor (BAFF), whereas removal of terminal sialic acid on plasma cells further potentiated the ligand-mediated protection. This effect is associated with the increased surface retention of BCMA, leading to its elevated level on cell surface. In addition, the α1-3,-4 fucosylation, but not the terminal sialylation, assists the binding of BCMA with ligands in an in vitro binding assay. Together, our results highlight the importance of N-glycosylation on BCMA in the regulation of ligand binding and functions of plasma cells.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Han-Wen
authors.initials: HW
authors.lastname: Huang
authors.forename: Chein-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Kuo-I
authors.initials: KI
authors.lastname: Lin
mesh_terms: D001216:Asparagine / Q000737:chemistry; D053301:B-Cell Maturation Antigen / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D057930:Click Chemistry; D006031:Glycosylation; D006801:Humans; D008024:Ligands; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011134:Polysaccharides / Q000737:chemistry* / Q000502:physiology*
chemical_list: D053301:B-Cell Maturation Antigen; D008024:Ligands; D011134:Polysaccharides; D001216:Asparagine