Mechanisms Underlying B-cell Tolerance Induction by Antigen–Immunoglobulin G Gene Transfer

Abstract

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 antigen-presenting 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.