B-Lymphocyte Phenotype Determines T-Lymphocyte Subset Differentiation in Autoimmune Diabetes.

Authors

Leire Egia-Mendikute
Berta Arpa
Estela Rosell-Mases
Marta Corral-Pujol
Jorge Carrascal
Jorge Carrillo
Conchi Mora
Harry Chapman, The Jackson LaboratoryFollow
Anaïs Panosa
Marta Vives-Pi
Thomas Stratmann
David V. Serreze, The Jackson LaboratoryFollow
Joan Verdaguer

Document Type

Article

Publication Date

7-25-2019

Keywords

JMG

JAX Source

Front Immunol 2019 Jul 25; 10:1732

Volume

10

First Page

1732

Last Page

1732

ISSN

1664-3224

PMID

31428087

DOI

https://doi.org/10.3389/fimmu.2019.01732

Grant

DK46266,DK95735,Juvenile Diabetes Research Foundation,American Diabetes Association,Helmsley Charitable Trust

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-K^d and H2-A^g7 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.

Comments

We thank Dr. Jeremy Racine and Mr. Qiming Wang for reviewing the manuscript. Special thanks to Ms. D. Cullell-Young for English grammar assistance.

Recommended Citation

Egia-Mendikute L, Arpa B, Rosell-Mases E, Corral-Pujol M, Carrascal J, Carrillo J, Mora C, Chapman H, Panosa A, Vives-Pi M, Stratmann T, Serreze DV, Verdaguer J. B-Lymphocyte Phenotype Determines T-Lymphocyte Subset Differentiation in Autoimmune Diabetes. Front Immunol 2019 Jul 25; 10:1732