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

Although the autoimmune destruction of pancreatic β-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 ef...

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Autores principales: Leeth, Caroline M., Racine, Jeremy, Chapman, Harold D., Arpa, Berta, Carrillo, Jorge, Carrascal, Jorge, Wang, Qiming, Ratiu, Jeremy, Egia-Mendikute, Leire, Rosell-Mases, Estela, Stratmann, Thomas, Verdaguer, Joan, Serreze, David V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915583/
https://www.ncbi.nlm.nih.gov/pubmed/26961115
http://dx.doi.org/10.2337/db15-1606
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author Leeth, Caroline M.
Racine, Jeremy
Chapman, Harold D.
Arpa, Berta
Carrillo, Jorge
Carrascal, Jorge
Wang, Qiming
Ratiu, Jeremy
Egia-Mendikute, Leire
Rosell-Mases, Estela
Stratmann, Thomas
Verdaguer, Joan
Serreze, David V.
author_facet Leeth, Caroline M.
Racine, Jeremy
Chapman, Harold D.
Arpa, Berta
Carrillo, Jorge
Carrascal, Jorge
Wang, Qiming
Ratiu, Jeremy
Egia-Mendikute, Leire
Rosell-Mases, Estela
Stratmann, Thomas
Verdaguer, Joan
Serreze, David V.
author_sort Leeth, Caroline M.
collection PubMed
description Although the autoimmune destruction of pancreatic β-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 β-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 β-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.
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spelling pubmed-49155832017-07-01 B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice Leeth, Caroline M. Racine, Jeremy Chapman, Harold D. Arpa, Berta Carrillo, Jorge Carrascal, Jorge Wang, Qiming Ratiu, Jeremy Egia-Mendikute, Leire Rosell-Mases, Estela Stratmann, Thomas Verdaguer, Joan Serreze, David V. Diabetes Immunology and Transplantation Although the autoimmune destruction of pancreatic β-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 β-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 β-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. American Diabetes Association 2016-07 2016-03-09 /pmc/articles/PMC4915583/ /pubmed/26961115 http://dx.doi.org/10.2337/db15-1606 Text en © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Immunology and Transplantation
Leeth, Caroline M.
Racine, Jeremy
Chapman, Harold D.
Arpa, Berta
Carrillo, Jorge
Carrascal, Jorge
Wang, Qiming
Ratiu, Jeremy
Egia-Mendikute, Leire
Rosell-Mases, Estela
Stratmann, Thomas
Verdaguer, Joan
Serreze, David V.
B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice
title B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice
title_full B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice
title_fullStr B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice
title_full_unstemmed B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice
title_short B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice
title_sort b-lymphocytes expressing an ig specificity recognizing the pancreatic β-cell autoantigen peripherin are potent contributors to type 1 diabetes development in nod mice
topic Immunology and Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915583/
https://www.ncbi.nlm.nih.gov/pubmed/26961115
http://dx.doi.org/10.2337/db15-1606
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