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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1998-11-4
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pubmed:abstractText |
We examined the role of c-Fos in the differentiation of mature B cells into IgG-producing cells using transgenic mice carrying the c-fos gene under the control of the IFN-alpha/beta-inducible Mx promoter (Mx-c-fos) or the constitutive H-2Kb promoter (H2-c-fos). Splenic B cells from Mx-c-fos mice were cultured with LPS and rIL-4, and IgG1+ B cells were developed in the culture after day 3. When IFN-alpha/beta was added to the culture from day 2, development of IgG1+ B cells was perturbed, and the number of apoptotic cells increased within 24 h, suggesting that c-Fos induces apoptosis in Ig class-switching B cells. To confirm the effect of c-Fos on B cell differentiation in vivo, H2-c-fos mice were immunized with DNP-OVA. The mice produced primary IgM, but not IgG, anti-DNP Ab in serum and failed to generate germinal centers in spleen. The perturbation of germinal center formation in H2-c-fos mice was rescued by mating them with transgenic mice carrying the bcl-2 gene with the Ig promoter. However, primary IgG1 anti-DNP Ab production was still suppressed in doubly transgenic mice, suggesting that Bcl-2 can delay the time of c-Fos-induced apoptosis in Ig class-switching B cells but cannot rescue the death. Since c-Fos is induced in mature B cells reacted with Ags, and clonal deletion of self-reactive B cells in germinal centers is insensitive to Bcl-2, these results suggest that c-Fos plays a causal role in clonal deletion of germinal center B cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
161
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3853-61
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9780150-Animals,
pubmed-meshheading:9780150-Apoptosis,
pubmed-meshheading:9780150-B-Lymphocytes,
pubmed-meshheading:9780150-Gene Expression Regulation,
pubmed-meshheading:9780150-Genes, fos,
pubmed-meshheading:9780150-Germinal Center,
pubmed-meshheading:9780150-Interferon-alpha,
pubmed-meshheading:9780150-Interferon-beta,
pubmed-meshheading:9780150-Mice,
pubmed-meshheading:9780150-Mice, Inbred C57BL,
pubmed-meshheading:9780150-Mice, Transgenic,
pubmed-meshheading:9780150-Proto-Oncogene Proteins c-fos
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pubmed:year |
1998
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pubmed:articleTitle |
c-Fos induces apoptosis in germinal center B cells.
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pubmed:affiliation |
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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