B-Lymphocyte Phenotype Determines T-Lymphocyte Subset Differentiation in Autoimmune Diabetes
Egia-Mendikute, Leire (Institut de Recerca Biomèdica de Lleida)
Arpa, Berta (Institut de Recerca Biomèdica de Lleida)
Rosell-Mases, Estela (Institut de Recerca Biomèdica de Lleida)
Corral Pujol, Marta (Institut de Recerca Biomèdica de Lleida)
Carrascal, Jorge (Institut de Recerca Biomèdica de Lleida)
Carrillo, Jorge (Institut de Recerca Biomèdica de Lleida)
Mora, Conchi (Institut de Recerca Biomèdica de Lleida)
Chapman, Harold (Jackson Laboratory)
Panosa, Anaïs (Institut de Recerca Biomèdica de Lleida)
Vives Pi, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Stratmann, Thomas (Universitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia)
Serreze, David (Jackson Laboratory)
Verdaguer, Joan (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)

Date:	2019
Abstract:	Previous studies indicate that B-lymphocytes play a key role activating diabetogenic T-lymphocytes during the development of autoimmune diabetes. Recently, two transgenic NOD mouse models were generated: the NOD-PerIg and the 116C-NOD mice. In NOD-PerIg mice, B-lymphocytes acquire an activated proliferative phenotype and support accelerated autoimmune diabetes development. In contrast, in 116C-NOD mice, B-lymphocytes display an anergic-like phenotype delaying autoimmune diabetes onset and decreasing disease incidence. The present study further evaluates the T- and B-lymphocyte phenotype in both models. In islet-infiltrating B-lymphocytes (IIBLs) from 116C-NOD mice, the expression of H2-Kd and H2-Ag7 is decreased, whereas that of BAFF, BAFF-R, and TACI is increased. In contrast, IIBLs from NOD-PerIg show an increase in CD86 and FAS expression. In addition, islet-infiltrating T-lymphocytes (IITLs) from NOD-PerIg mice exhibit an increase in PD-1 expression. Moreover, proliferation assays indicate a high capacity of B-lymphocytes from NOD-PerIg mice to secrete high amounts of cytokines and induce T-lymphocyte activation compared to 116C B-lymphocytes. This functional variability between 116C and PerIg B-lymphocytes ultimately results in differences in the ability to shape T-lymphocyte phenotype. These results support the role of B-lymphocytes as key regulators of T-lymphocytes in autoimmune diabetes and provide essential information on the phenotypic characteristics of the T- and B-lymphocytes involved in the autoimmune response in autoimmune diabetes.
Grants:	Agencia Estatal de Investigación SAF2016-77227-R Instituto de Salud Carlos III CIBERDEM/5-2005-1133 Ministerio de Educación y Ciencia BES-2007-15221
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Type 1 diabetes ; NOD mouse ; Transgenic mouse model ; B-lymphocyte phernotype ; T-lymphocyte phernotype
Published in:	Frontiers in immunology, Vol. 10 (2019) , p. 1732, ISSN 1664-3224

DOI: 10.3389/fimmu.2019.01732
PMID: 31428087

11 p, 5.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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