Enhanced responsiveness to T-cell help causes loss of B-lymphocyte tolerance to a ß-cell neo-self-antigen in type 1 diabetes prone NOD mice.
Eur J Immunol
; 40(12): 3413-25, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-21108464
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 ß-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).
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoglobulinas
/
Linfocitos B
/
Linfocitos T Colaboradores-Inductores
/
Diabetes Mellitus Tipo 1
/
Células Secretoras de Insulina
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Alemania