| First Author | Silveira PA | Year | 2004 |
| Journal | J Immunol | Volume | 172 |
| Issue | 8 | Pages | 5086-94 |
| PubMed ID | 15067092 | Mgi Jnum | J:89156 |
| Mgi Id | MGI:3038572 | Doi | 10.4049/jimmunol.172.8.5086 |
| Citation | Silveira PA, et al. (2004) B cell selection defects underlie the development of diabetogenic APCs in nonobese diabetic mice. J Immunol 172(8):5086-94 |
| abstractText | 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. |
