| 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. | |
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MedLine Citation:
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PMID: 21108464 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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). |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-11 |
Journal Detail:
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Title: European journal of immunology Volume: 40 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 3413-25 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Immunology Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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