Document Detail


Potential role of CARMA1 in CD40-induced splenic B cell proliferation and marginal zone B cell maturation.
MedLine Citation:
PMID:  17048267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
NF-kappaB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen-mediated activation of B cells. CARD domain and MAGUK-domain containing protein-1 (CARMA1), recently identified adaptor molecule, has been shown to play an essential role in BCR-induced NF-kappaB activation. CARMA1-deficient B cells fail to proliferate upon BCR stimulation, leading to defective humoral responses. Surprisingly, CARMA1-deficient B cells are also defective in CD40-induced proliferation. The mechanisms responsible for CD40-induced proliferation defect have not yet been characterized. In this study, we show that signaling cascades activated by CD40 stimulation are largely unaffected in CARMA1-deficient B cells. Instead, we have found that the defective proliferation of CARMA1-deficient B cells is due to two events. First, CARMA1-deficient B cells show defective cell-cycle progression. Secondly, the numbers of marginal zone (MZ) B cells, which are the main responders upon CD40 stimulation, are greatly diminished in CARMA1-deficient mice. Since B cell maturation requires basal signaling through BCR and NF-kappaB activation, we propose that impaired BCR signaling in CARMA1-deficient mice leads to defective maturation of MZ B cell population, which in turn, contributes to impaired proliferation upon CD40 stimulation.
Authors:
Bhanu P Pappu; Xin Lin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  36     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-13     Completed Date:  2007-01-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3033-43     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD40 / immunology*,  pharmacology
Apoptosis
Apoptosis Regulatory Proteins / genetics,  physiology*
B-Lymphocytes / cytology,  drug effects,  immunology*
CARD Signaling Adaptor Proteins / genetics,  physiology*
Cell Cycle / drug effects
Cell Movement
Cell Proliferation
Lymphocyte Activation / genetics
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase Kinases / metabolism
NF-kappa B / agonists
Spleen / cytology,  drug effects,  immunology*
Grant Support
ID/Acronym/Agency:
GM065899/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD40; 0/Apoptosis Regulatory Proteins; 0/CARD Signaling Adaptor Proteins; 0/Card11 protein, mouse; 0/NF-kappa B; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases

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