B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic beta-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice

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dc.contributor.authorLeeth, Caroline M.en
dc.contributor.authorRacine, Jeremyen
dc.contributor.authorChapman, Harold D.en
dc.contributor.authorArpa, Bertaen
dc.contributor.authorCarrillo, Jorgeen
dc.contributor.authorCarrascal, Jorgeen
dc.contributor.authorWang, Qimingen
dc.contributor.authorRatiu, Jeremyen
dc.contributor.authorEgia-Mendikute, Leireen
dc.contributor.authorRosell-Mases, Estelaen
dc.contributor.authorStratmann, Thomasen
dc.contributor.authorVerdaguer, Joanen
dc.contributor.authorSerreze, David V.en
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2017-07-28T18:36:36Zen
dc.date.available2017-07-28T18:36:36Zen
dc.date.issued2016-07-01en
dc.description.abstractAlthough the autoimmune destruction of pancreatic b-cells underlying type 1 diabetes (T1D) development is ultimately mediated by T cells in NOD mice and also likely in humans, B cells play an additional key pathogenic role. It appears that the expression of plasma membrane–bound Ig molecules that efficiently capture b-cell antigens allows autoreactive B cells that bypass normal tolerance induction processes to be the subset of antigen-presenting cells most efficiently activating diabetogenic T cells. NOD mice transgenically expressing Ig molecules recognizing antigens that are (insulin) or are not (hen egg lysozyme [HEL]) expressed by b-cells have proven useful in dissecting the developmental basis of diabetogenic B cells. However, these transgenic Ig specificities were originally selected for their ability to recognize insulin or HEL as foreign, rather than autoantigens. Thus, we generated and characterized NOD mice transgenically expressing an Ig molecule representative of a large proportion of naturally occurring islet-infiltrating B cells in NOD mice recognizing the neuronal antigen peripherin. Transgenic peripherin-autoreactive B cells infiltrate NOD pancreatic islets, acquire an activated proliferative phenotype, and potently support accelerated T1D development. These results support the concept of neuronal autoimmunity as a pathogenic feature of T1D, and targeting such responses could ultimately provide an effective disease intervention approach.en
dc.description.versionPublished versionen
dc.format.extent1977 - 1987 (11) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.2337/db15-1606en
dc.identifier.eissn1939-327Xen
dc.identifier.issn0012-1797en
dc.identifier.issue7en
dc.identifier.orcidLeeth, CM [0000-0002-5909-7623]en
dc.identifier.urihttp://hdl.handle.net/10919/78462en
dc.identifier.volume65en
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000378463000024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectEndocrinology & Metabolismen
dc.subjectINTERMEDIATE-FILAMENT PROTEINen
dc.subjectANTIGEN-PRESENTING CELLSen
dc.subjectANTIBODY PREVENTSen
dc.subjectINITIATIONen
dc.subjectINSULITISen
dc.subjectDESTRUCTIONen
dc.subjectDEPLETIONen
dc.subjectTOLERANCEen
dc.subjectSUBSETSen
dc.subjectANERGYen
dc.titleB-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic beta-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Miceen
dc.title.serialDiabetesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen

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