title: Peripherin is a relevant neuroendocrine autoantigen recognized by islet-infiltrating B lymphocytes.
abstract: Most of our knowledge of the antigenic repertoire of autoreactive B lymphocytes in type 1 diabetes (T1D) comes from studies on the antigenic specificity of both circulating islet-reactive autoantibodies and peripheral B lymphocyte hybridomas generated from human blood or rodent spleen. In a recent study, we generated hybridoma cell lines of infiltrating B lymphocytes from different mouse strains developing insulitis, but with different degrees of susceptibility to T1D, to characterize the antigenic specificity of islet-infiltrating B lymphocytes during progression of the disease. We found that many hybridomas produced mAbs restricted to the peripheral nervous system (PNS), thus indicating an active B lymphocyte response against PNS elements in the pancreatic islet during disease development. The aim of this study was to identify the autoantigen recognized by these anti-PNS mAbs. Our results showed that peripherin is the autoantigen recognized by all anti-PNS mAbs, and, therefore, a relevant neuroendocrine autoantigen targeted by islet-infiltrating B lymphocytes. Moreover, we discovered that the immune dominant epitope of this B lymphocyte immune response is found at the C-terminal end of Per58 and Per61 isoforms. In conclusion, our study strongly suggests that peripherin is a major autoantigen targeted during T1D development and poses a new question on why peripherin-specific B lymphocytes are mainly attracted to the islet during disease.
authors.affiliation: Laboratory of Immunobiology for Research and Diagnosis and Center for Transfusion and Tissue Bank; Institut d'Investigacio Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Puertas
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrillo
authors.forename: Xavier
authors.initials: X
authors.lastname: Pastor
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Ampudia
authors.forename: Raquel
authors.initials: R
authors.lastname: Planas
authors.forename: Aurora
authors.initials: A
authors.lastname: Alba
authors.forename: Roxana
authors.initials: R
authors.lastname: Bruno
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Estanyol
authors.forename: Marta
authors.initials: M
authors.lastname: Vives-Pi
authors.forename: Joan
authors.initials: J
authors.lastname: Verdaguer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D006825:Hybridomas; D007340:Insulinoma / Q000276:immunology / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000276:immunology* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism*; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D064531:Peripherins; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D010446:Peptide Fragments; D064531:Peripherins; D020033:Protein Isoforms