| Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo. | |
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MedLine Citation:
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PMID: 21518858 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Extrafollicular (EF) B-cell responses are increasingly being recognized as an alternative pathway of B-cell activation, particularly in autoimmunity. Critical cellular interactions required for the EF B-cell response are unclear. A key question in autoimmunity, in which Toll-like receptor (TLR) signals are costimulatory and could be sufficient for B-cell activation, is whether T cells are required for the response. This is pivotal, because autoreactive B cells are considered antigen-presenting cells for autoreactive T cells, but where such interactions occur has not been identified. Here, using AM14 site-directed transgenic rheumatoid factor (RF) mice, we report that B cells can be activated, differentiate, and isotype-switch independent of antigen-specific T-cell help, αβ T cells, CD40L signaling, and IL-21 signaling to B cells. However, T cells do dramatically enhance the response, and this occurs via CD40L and IL-21 signals. Surprisingly, the response is completely inducible T-cell costimulator ligand independent. These results establish that, although not required, T cells substantially amplify EF autoantibody production and thereby implicate T-independent autoreactive B cells as a potential vector for breaking T-cell tolerance. We suggest that these findings explain why autoreactivity first focuses on self-components for which B cells carry TLR ligands, because these will uniquely be able to activate B cells independently of T cells, with subsequent T-B interactions activating autoreactive T cells, resulting in chronic autoimmunity. |
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Authors:
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Rebecca A Sweet; Michelle L Ols; Jaime L Cullen; Ashley Viehmann Milam; Hideo Yagita; Mark J Shlomchik |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-04-25 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-11 Completed Date: 2011-07-15 Revised Date: 2011-11-10 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 7932-7 Citation Subset: IM |
Affiliation:
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Department of Immunobiology and Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adoptive Transfer Animals Autoimmunity* B-Lymphocytes / immunology* Ligands Lymphocyte Activation Lymphocyte Cooperation / immunology Lymphopenia / immunology Mice Mice, Inbred BALB C Mice, Knockout Mice, Transgenic Receptors, Antigen, T-Cell, alpha-beta / deficiency, genetics Rheumatoid Factor / immunology Signal Transduction / immunology T-Lymphocytes / immunology* Toll-Like Receptors / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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1F31AI071694-01/AI/NIAID NIH HHS; R01 AI073722-05/AI/NIAID NIH HHS; R01-AI43603/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Toll-Like Receptors; 9009-79-4/Rheumatoid Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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