Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-11-22
pubmed:abstractText
During the adaptive phase of an immune response, naive B cells receive multiple signals to become activated. Among them are the engagement of the B cell Ag receptor and stimulation by cytokines. Specifically for an anti-microbial response, the recognition of viral or bacterial Ags by the BCR and the stimulation of IFN-gamma result in the predominant production of IgG2a. The T-bet protein has been shown to be required for class switching to IgG2a. In this report we further investigated the regulation of T-bet gene expression during the early stage of B cell activation. We show that there is a striking synergistic activation of T-bet in primary B cells when both the BCR and IFN-gamma signaling pathways are activated. The synergistic activation of T-bet correlates with a 100% increase in the number of B cells that produce IgG2a. This transcription synergy on T-bet is transient in the first 24 h of B cell activation. Furthermore, we demonstrate that the synergistic activation of T-bet is dependent on Stat1 and that Stat1 is required for the IgG2a germline transcription and the production of IgG2a in response to the simultaneous signaling of BCR and IFN-gamma. Finally, we show that Stat1 directly regulates the expression of T-bet by binding to the T-bet promoter. These results reveal the mechanism of regulation of T-bet expression and uncover a novel physiological function of Stat1 for B cell activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7419-24
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16301649-Animals, pubmed-meshheading:16301649-B-Lymphocytes, pubmed-meshheading:16301649-Blotting, Western, pubmed-meshheading:16301649-Electrophoretic Mobility Shift Assay, pubmed-meshheading:16301649-Flow Cytometry, pubmed-meshheading:16301649-Gene Expression, pubmed-meshheading:16301649-Gene Expression Regulation, pubmed-meshheading:16301649-Immunoglobulin Class Switching, pubmed-meshheading:16301649-Immunoglobulin G, pubmed-meshheading:16301649-Interferon-gamma, pubmed-meshheading:16301649-Lymphocyte Activation, pubmed-meshheading:16301649-Mice, pubmed-meshheading:16301649-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16301649-STAT1 Transcription Factor, pubmed-meshheading:16301649-T-Box Domain Proteins, pubmed-meshheading:16301649-Transcription Factors
pubmed:year
2005
pubmed:articleTitle
Stat1-dependent synergistic activation of T-bet for IgG2a production during early stage of B cell activation.
pubmed:affiliation
Department of Pathology and Molecular Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural