Original Research ARTICLE
B-lymphocyte phenotype determines T-lymphocyte subset differentiation in autoimmune diabetes
- 1Department of Experimental Medicine, Faculty of Medicine, University of Lleida, Spain
- 2Biomedical Research Center in Diabetes Network and Associated Metabolic Diseases (CIBERDEM), Spain
- 3Jackson Laboratory, United States
- 4Lleida Institute for Biomedical Research (IRBLleida), Spain
- 5Germans Trias i Pujol Health Science Research Institute (IGTP), Spain
- 6Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain
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.
Keywords: Type 1 diabetes (T1D), NOD mouse model, Transgenic mouse model of human disease, B-lymphocyte phenotype, T-lymphocyte phenotype
Received: 28 Dec 2018;
Accepted: 09 Jul 2019.
Edited by:Urs Christen, Goethe University Frankfurt, Germany
Reviewed by:Ezio Bonifacio, Dresden University of Technology, Germany
Kathryn Haskins, School of Medicine, University of Colorado Denver, United States
Thomas W. Kay, St Vincents Institute of Medical Research, Australia
Copyright: © 2019 Verdaguer Autonell, Egia Mendikute, Arpa Puigdemont, Rosell Mases, Corral Pujol, Carrascal Sánchez, Carrillo Molina, Mora Giral, Chapman, Panosa, Vives-Pi, Stratmann and Serreze. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD, PhD. Joan Verdaguer Autonell, Department of Experimental Medicine, Faculty of Medicine, University of Lleida, Lleida, Catalonia, Spain, firstname.lastname@example.org