TY - JOUR
T1 - B-Lymphocyte Phenotype Determines T-Lymphocyte Subset Differentiation in Autoimmune Diabetes
AU - Egia-Mendikute, Leire
AU - Arpa, Berta
AU - Rosell-Mases, Estela
AU - Corral-Pujol, Marta
AU - Carrascal, Jorge
AU - Carrillo, Jorge
AU - Mora, Conchi
AU - Chapman, Harold
AU - Panosa, Anaïs
AU - Vives-Pi, Marta
AU - Stratmann, Thomas
AU - Serreze, David
AU - Verdaguer, Joan
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - B-lymphocyte phernotype
KW - NOD mouse
KW - T-lymphocyte phernotype
KW - transgenic mouse model
KW - type 1 diabetes
U2 - https://doi.org/10.3389/fimmu.2019.01732
DO - https://doi.org/10.3389/fimmu.2019.01732
M3 - Article
C2 - 31428087
VL - 10
SP - 1732
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
ER -
