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Enhanced responsiveness to T-cell help causes loss of B-lymphocyte tolerance to a β-cell neo-self-antigen in type 1 diabetes prone NOD mice.
MedLine Citation:
PMID:  21108464     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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 β-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).
Authors:
Selwyn Lewis Cox; Jessica Stolp; Nicole L Hallahan; Jacqueline Counotte; Wenyu Zhang; David V Serreze; Antony Basten; Pablo A Silveira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-11
Journal Detail:
Title:  European journal of immunology     Volume:  40     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3413-25     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Immunology Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
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