title: Neither B lymphocytes nor antibodies directed against self antigens of the islets of Langerhans are required for development of virus-induced autoimmune diabetes.
abstract: We evaluated the role of the humoral arm of the immune response in causing or contributing to virus-induced diabetes. Transgenic mice expressing the nucleoprotein (NP) or glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter (RIP) in pancreatic beta cells (RIP-LCMV) and RIP-LCMV mice with genetic dysfunction of B cells (RIP-LCMV x microMT/microMT) were compared for development of diabetes after challenge with LCMV. After inoculation with LCMV, B and T lymphocytes and macrophages infiltrated into pancreatic islets in RIP-LCMV mice, and over 50% of these mice generated Abs against host insulin or glutamate decarboxylase. However, neither B cells nor the autoantibodies played a direct role in the initiation, kinetics, or severity of the virus-induced diabetes as judged by comparing disease in RIP-LCMV mice to littermates whose functional B cells were genetically eliminated. Furthermore, the quality and quantity of T lymphocyte and macrophage infiltration was similar in the B cell-deficient and non-B cell-deficient RIP-LCMV mice. Although the development of autoantibodies to islet Ags had no direct influence on the pathogenesis of insulin-dependent (type 1) diabetes mellitus, it served as a prediabetes marker, as such autoantibodies were often elevated before the onset of disease. Hence, the RIP-LCMV model is not only useful for understanding the pathogenetic mechanisms of how islets are destroyed and spared but also for evaluating therapeutic strategies before onset of clinical diabetes.
authors.affiliation: Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. aholz@scripps.edu
authors.forename: A
authors.initials: A
authors.lastname: Holz
authors.forename: T
authors.initials: T
authors.lastname: Dyrberg
authors.forename: W
authors.initials: W
authors.lastname: Hagopian
authors.forename: D
authors.initials: D
authors.lastname: Homann
authors.forename: M
authors.initials: M
authors.lastname: von Herrath
authors.forename: M B
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000208:Acute Disease; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D007328:Insulin / Q000235:genetics / Q000276:immunology; D007515:Islets of Langerhans / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007328:Insulin; D005968:Glutamate Decarboxylase