| Impaired apoptotic cell clearance in the germinal center by Mer-deficient tingible body macrophages leads to enhanced antibody-forming cell and germinal center responses. | |
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MedLine Citation:
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PMID: 20952679 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Germinal centers (GCs) are specialized microenvironments that generate high-affinity Ab-forming cells (AFCs) and memory B cells. Many B cells undergo apoptosis during B cell clonal selection in GCs. Although the factors that regulate the AFC and GC responses are not precisely understood, it is widely believed that dysregulated AFCs and GCs contribute to autoimmunity. The Mer receptor tyrosine kinase (Mer) facilitates macrophage clearance of apoptotic cells. The Tyro-3, Axl, and Mer receptors, including Mer, suppress TLRs and cytokine-mediated inflammatory responses. We report in this study that tingible body macrophages (TBMφs) in GCs express Mer. Compared to C57BL/6 (B6) controls, Mer-deficient (Mer(-/-)) mice had significantly higher AFC, GC, and Th1-skewed IgG2 Ab (especially IgG2c) responses against the T cell-dependent Ag (4-hydroxy-3-nitrophenyl) acetyl-chicken γ globulin. Mer(-/-) mice had a significantly higher percentage of GC B cells on days 9, 14, and 21 postimmunization compared with B6 controls. Significantly increased numbers of apoptotic cells accumulated in Mer(-/-) GCs than in B6 GCs, whereas the number of TBMφs remained similar in both strains. Our data are the first, to our knowledge, to demonstrate a critical role for Mer in GC apoptotic cell clearance by TBMφs and have interesting implications for Mer in the regulation of B cell tolerance operative in the AFC and GC pathways. |
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Authors:
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Ziaur S M Rahman; Wen-Hai Shao; Tahsin N Khan; Yuxuan Zhen; Philip L Cohen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-15 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-04 Completed Date: 2010-12-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 5859-68 Citation Subset: AIM; IM |
Affiliation:
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Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107-5541, USA. zrahman@mail.jci.tju.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibody Formation / immunology Antibody-Producing Cells / immunology*, metabolism Apoptosis / immunology* Cell Separation Enzyme-Linked Immunosorbent Assay Flow Cytometry Germinal Center / cytology, immunology Immunohistochemistry In Situ Nick-End Labeling Macrophages / immunology*, metabolism Mice Mice, Inbred C57BL Mice, Knockout Proto-Oncogene Proteins / immunology*, metabolism Receptor Protein-Tyrosine Kinases / immunology*, metabolism Spleen / cytology, immunology |
| Grant Support | |
ID/Acronym/Agency:
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AR055701/AR/NIAMS NIH HHS; R01DE017590/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Proto-Oncogene Proteins; EC 2.7.1.112/Mertk protein, mouse; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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