Document Detail


Regulation of B-cell entry into the cell cycle.
MedLine Citation:
PMID:  18759927     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
B cells are induced to enter the cell cycle by stimuli including ligation of the B-cell receptor (BCR) complex and Toll-like receptor (TLR) agonists. This review discusses the contribution of several molecules, which act at distinct steps in B-cell activation. The adapter molecule Bam32 (B-lymphocyte adapter of 32 kDa) helps promote BCR-induced cell cycle entry, while the secondary messenger superoxide has the opposite effect. Bam32 and superoxide may fine tune BCR-induced activation by competing for the same limited resources, namely Rac1 and the plasma membrane phospholipid PI(3,4)P(2). The co-receptor CD22 can inhibit BCR-induced proliferation by binding to novel CD22 ligands. Finally, regulators of B-cell survival and death also play roles in B-cell transit through the cell cycle. Caspase 6 negatively regulates CD40- and TLR-dependent G(1) entry, while acting later in the cell cycle to promote S-phase entry. Caspase 6 deficiency predisposes B cells to differentiate rather than proliferate after stimulation. Bim, a pro-apoptotic Bcl-2 family member, exerts a positive regulatory effect on cell cycle entry, which is opposed by Bcl-2. New insights into what regulates B-cell transit through the cell cycle may lead to thoughtful design of highly selective drugs that target pathogenic B cells.
Authors:
Sabrina Richards; Chie Watanabe; Lorna Santos; Andrew Craxton; Edward A Clark
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  224     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-09-01     Completed Date:  2008-11-03     Revised Date:  2011-05-12    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  183-200     Citation Subset:  IM    
Affiliation:
Department of Immunology and Microbiology, University of Washington, Seattle, WA 98195, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / immunology,  metabolism
Animals
Antigens, CD22 / metabolism
Apoptosis Regulatory Proteins / immunology*
B-Lymphocytes / cytology*,  immunology*,  metabolism
Cell Cycle / immunology*
Cell Proliferation
Cell Survival / immunology
Humans
Lymphocyte Activation / immunology
NADPH Oxidase / immunology,  metabolism
Receptors, Antigen, B-Cell / immunology,  metabolism*
Signal Transduction / immunology
Grant Support
ID/Acronym/Agency:
AI44250/AI/NIAID NIH HHS; AI52203/AI/NIAID NIH HHS; DE16381/DE/NIDCR NIH HHS; GM37905/GM/NIGMS NIH HHS; R01 DE016381-04/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD22; 0/Apoptosis Regulatory Proteins; 0/DAPP1 protein, human; 0/Receptors, Antigen, B-Cell; EC 1.6.3.1/NADPH Oxidase
Comments/Corrections

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