| First Author | Cox SL | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 12 | Pages | 3413-25 |
| PubMed ID | 21108464 | Mgi Jnum | J:174579 |
| Mgi Id | MGI:5139987 | Doi | 10.1002/eji.201040817 |
| Citation | Cox SL, et al. (2010) Enhanced responsiveness to T-cell help causes loss of B-lymphocyte tolerance to a beta-cell neo-self-antigen in type 1 diabetes prone NOD mice. Eur J Immunol 40(12):3413-25 |
| abstractText | Self-reactive B lymphocytes contribute to type 1 diabetes pathogenesis as APC and auto-Ab producers in NOD mice and humans. To shed light on the mechanisms responsible for the breakdown in B-lymphocyte self-tolerance to beta-cell Ag, we utilised a model whereby hen-egg lysozyme (HEL)-specific Ig Tg (IgHEL-Tg)-Tg B lymphocytes were allowed to develop in or were transferred into mice expressing the HEL Tg under an insulin promoter (insHEL-Tg). IgHEL-Tg B lymphocytes enhanced type 1 diabetes susceptibility of insHEL-Tg NOD mice. A comparison of the tolerogenic activity of IgHEL-Tg B lymphocytes with NOD and non-autoimmune-prone C57BL/6 genetic backgrounds showed that both were rendered anergic in the presence of insHEL when competing with polyclonal B lymphocytes. Nevertheless, NOD IgHEL-Tg B lymphocytes transferred into insHEL-Tg mice were more readily susceptible to rescue from anergy than their C57BL/6 counterparts, following provision of in vivo T-cell help. The different tolerogenic outcomes were an intrinsic property of B lymphocytes rather than being related to the quality of T-cell help, with the defective response being at least partially controlled by genes mapping to insulin-dependent diabetes (Idd) susceptibility loci on Chromosome 1 (Idd5) and 4 (Idd9/11). |
