B cell selection defects underlie the development of diabetogenic APCs in nonobese diabetic mice.
Document Type
Article
Publication Date
2004
Keywords
Antigen-Presenting-Cells, Autoantigens, B-Lymphocyte-Subsets, Cell-Differentiation, Clonal-Anergy, Clonal-Deletion, Diabetes-Mellitus-Type-I, Female, Membrane-Proteins, Mice, Mice-Inbred-C57BL, Mice-Inbred-NOD, Mice-Transgenic, RNA-Editing, Receptors-Antigen-T-Cell, Solubility
First Page
5086
Last Page
5094
JAX Source
J Immunol 2004 Apr; 172(8):5086-94.
Abstract
One mechanism whereby B cells contribute to type 1 diabetes in nonobese diabetic (NOD) mice is as a subset of APCs that preferentially presents MHC class II-bound pancreatic beta cell Ags to autoreactive CD4 T cells. This results from their ability to use cell surface Ig to specifically capture beta cell Ags. Hence, we postulated a diabetogenic role for defects in the tolerance mechanisms normally blocking the maturation and/or activation of B cells expressing autoreactive Ig receptors. We compared B cell tolerance mechanisms in NOD mice with nonautoimmune strains by using the IgHEL and Ig3-83 transgenic systems, in which the majority of B cells recognize one defined Ag. NOD- and nonautoimmune-prone mice did not differ in ability to delete or receptor edit B cells recognizing membrane-bound self Ags. However, in contrast to the nonautoimmune-prone background, B cells recognizing soluble self Ags in NOD mice did not undergo partial deletion and were also not efficiently anergized. The defective induction of B cell tolerance to soluble autoantigens is most likely responsible for the generation of diabetogenic APC in NOD mice.
Recommended Citation
Silveira PA,
Dombrowsky J,
Johnson E,
Chapman HD,
Nemazee D,
Serreze DV.
B cell selection defects underlie the development of diabetogenic APCs in nonobese diabetic mice. J Immunol 2004 Apr; 172(8):5086-94.