title: Analysis of IgM antibody production and repertoire in a mouse model of Sjögren's syndrome.
abstract: This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjögren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjögren's syndrome mouse model (Id3(-/-)). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells. We single-cell sorted B cells from the spleen, cervical lymph nodes, and submandibular gland tissue from Sjögren's syndrome mice and sequenced immunoglobulin M heavy-chain variable regions. Finally, autoantigen arrays were performed using immunoglobulin M derived from sera, cervical lymph nodes, spleens, and submandibular gland tissue of Id3(-/-) animals. Results suggest B cells from salivary tissue of Sjögren's syndrome mice are similar to those from secondary immune sites in terms of proliferative and secretory capacity. However, differences in repertoire usage, heavy chain complementarity-determining region 3 length, mutational frequency, and N region addition were observed among B cells derived from submandibular gland, cervical lymph node, and spleen tissue. Moreover, autoantigen array data show immunoglobulin M from salivary B cells have enriched specificity for Ro (Sjögren's syndrome A) and La (Sjögren's syndrome B). All together, these data suggest salivary B cells have unique repertoire characteristics that likely influence autoantigen binding and contribute to Sjögren's syndrome disease in a tissue-specific manner.
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA jkramer@buffalo.edu.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Kramer
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Nichol E
authors.initials: NE
authors.lastname: Holodick
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Vizconde
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Indu
authors.initials: I
authors.lastname: Raman
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Quan-Zhen
authors.initials: QZ
authors.lastname: Li
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gaile
authors.affiliation: *Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA; Division of Oral and Maxillofacial Pathology, Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA; Department of Oral Biology, School of Dental Medicine, and Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, USA; Department of Dental Medicine and Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA; and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rothstein
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D017422:Sequence Analysis, DNA; D059010:Single-Cell Analysis; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013363:Submandibular Gland / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D051796:Inhibitor of Differentiation Proteins; C067679:Idb3 protein, mouse
keywords: B cell repertoire; Id3−/−; salivary gland; sialadenitis