| Reduced c-myc expression levels limit follicular mature B cell cycling in response to TLR signals. | |
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MedLine Citation:
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PMID: 19299704 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The splenic B cell compartment is comprised of two major, functionally distinct, mature B cell subsets, i.e., follicular mature (FM) and marginal zone (MZ) B cells. Whereas MZ B cells exhibit a robust proliferative response following stimulation with the TLR4 ligand LPS, FM B cells display markedly delayed and reduced levels of proliferation to the identical stimulus. The current study was designed to identify a potential mechanism(s) accounting for this differential responsiveness. In contrast to the delay in cell cycle entry, FM and MZ B cells exhibited nearly identical LPS-driven alterations in the expression level of cell surface activation markers. Furthermore, both the NF-kappaB and mTOR signaling cascades were similarly activated by LPS stimulation in FM vs MZ B cells, while inducible activation of ERK and AKT were nearly absent in both subsets. MZ B cells, however, exhibited higher basal levels of phospho-AKT and pS6, consistent with a preactivated status. Importantly, both basal and LPS activation-induced c-myc expression was markedly reduced in FM vs MZ B cells and enforced c-myc expression fully restored the defective proliferative response in FM B cells. These data support a model wherein TLR responses in FM B cells are tightly regulated by limiting c-myc levels, thereby providing an important checkpoint to control nonspecific FM B cell activation in the absence of cognate Ag. |
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Authors:
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Almut Meyer-Bahlburg; Ashok D Bandaranayake; Sarah F Andrews; David J Rawlings |
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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 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 182 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-20 Completed Date: 2009-04-14 Revised Date: 2011-12-22 |
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: 4065-75 Citation Subset: AIM; IM |
Affiliation:
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Seattle Children's Research Institute, WA 98101, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / immunology*, metabolism Blotting, Western Carrier Proteins / immunology, metabolism Cell Cycle / immunology* Cell Proliferation Extracellular Signal-Regulated MAP Kinases / immunology, metabolism Flow Cytometry Gene Expression Lipopolysaccharides / immunology Lymphocyte Activation / immunology* Lymphocyte Subsets / immunology, metabolism Mice Mice, Inbred C57BL Mice, Transgenic NF-kappa B / immunology, metabolism Phosphotransferases (Alcohol Group Acceptor) / immunology, metabolism Proto-Oncogene Proteins c-akt / immunology, metabolism Proto-Oncogene Proteins c-myb / biosynthesis*, immunology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / immunology* Spleen / cytology, immunology TOR Serine-Threonine Kinases Toll-Like Receptors / immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA81140/CA/NCI NIH HHS; HD37091/HD/NICHD NIH HHS; HL075453/HL/NHLBI NIH HHS; R01 AI071163-05/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-myb; 0/Toll-Like Receptors; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
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