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

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.

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

“…It is postulated that B cells can act as APCs to stimulate CD4+ T cells, which in turn can release cytokines that promote cytotoxic CD8+ T cell-mediated destruction in the pancreas (reviewed in [ 47 , 48 , 49 ]). Egia-Mendikute et al show that autoreactive B cells shape T cell phenotype in an antigen-specific, transgenic NOD mouse model [ 50 ].…”

Inducible costimulator ligand (ICOSL) on CD19+ B cells is involved in immunopathological damage of rheumatoid arthritis (RA)

“…The recruitment of T/B lymphocytes recognizing a diverse repertoire of organ-specific autoantigens is reported to play an important role in the pathological process of RA ( 4 , 5 ). B lymphocytes, the principal participants of the humoral immunity, are generally recognized for their pleiotropic roles in secreting antibodies and presenting antigens to T cells ( 6 , 7 ). Nevertheless, the non-classical immune potential of B cell subsets, which can secrete a variety of proinflammatory cytokines, chemokines, and some important membrane molecules to mediate the immune response, has attracted more and more attention ( 4 , 5 , 7 – 9 ).…”