Mechanisms underlying B-cell tolerance induction by antigen-immunoglobulin G gene transfer.
Previous studies on the mechanisms underlying tolerance induction in diabetes have mainly focused on T cells, however B cells also have an important role in diabetes. Based on our previous studies that splenocytes, transduced with glutamic acid decarboxylase (GAD) 65 fused to immunoglobulin (Ig) G carrier, reduced antibody-mediated response in non-obese diabetic (NOD) mice, here we examined the mechanisms underlying B-cell tolerance in this system. We found that GAD-IgG-transduced splenocytes did not reduce CD40 expression on B-cells in NOD mice, but they did downregulate CD40 ligand (CD40L) expression. Furthermore, anti-CD40L injection reduced autoantibody levels in NOD mice and in vitro experiments demonstrated that CD40L blockade reduced the antigenpresenting capability of B-cells. In conclusion, the results of this study suggest that downregulation of CD40L may be one mechanism underlying the induction of B-cell tolerance in GAD-IgG-treated NOD mice.
Wang
R
R
Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
Wang
J
J
Han
G
G
Song
L
L
Chen
G
G
Xu
R
R
Yu
M
M
Qian
J
J
Shen
B
B
Li
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic
D019013:CD40 Antigens; D007074:Immunoglobulin G; D023201:CD40 Ligand; D005968:Glutamate Decarboxylase