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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-2-27
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pubmed:abstractText |
CD40 is essential for efficient humoral immune responses. CD40 has two cytoplasmic domains required for binding of tumor necrosis factor receptor-associated factors (TRAF). The TRAF6-binding site is within the membrane proximal cytoplasmic (Cmp) region, while a PXQXT motif in the membrane distal cytoplasmic (Cmd) region needs to engage TRAF2/3/5. To dissect CD40 signals necessary for B cell differentiation, we generated transgenic mice expressing wild-type and mutant human CD40 (hCD40) molecules in a mouse CD40-deficient (mCD40(-/-)) background. The B cell-specific expression of hCD40 in mCD40(-/-) mice resulted in T-dependent antibody responses including germinal center (GC) formation. Mutant hCD40 molecules that carry either a point mutation of the TRAF2/3/5-binding site or a deletion of the Cmd region rescued extrafollicular B cell differentiation but not GC formation. A mutant hCD40 that comprises of only the TRAF2/3/5-binding site in the cytoplasmic region also rescued low but significant titers of antigen-specific IgG1 without GC formation. These results demonstrated that two distinct signals either from the Cmp or from the Cmd region induced the extrafollicular B cell differentiation and Ig class switching; however, GC formation required both. We conclude that combinations of these two signals determine which of the extrafollicular or the follicular (GC) differentiation pathway B cells enter.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0953-8178
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
319-29
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11867568-Animals,
pubmed-meshheading:11867568-Antigens, CD40,
pubmed-meshheading:11867568-B-Lymphocytes,
pubmed-meshheading:11867568-Cell Differentiation,
pubmed-meshheading:11867568-Cell Membrane,
pubmed-meshheading:11867568-Germinal Center,
pubmed-meshheading:11867568-Immunoglobulin Class Switching,
pubmed-meshheading:11867568-Immunoglobulins,
pubmed-meshheading:11867568-Immunohistochemistry,
pubmed-meshheading:11867568-Mice,
pubmed-meshheading:11867568-Mice, Inbred Strains,
pubmed-meshheading:11867568-Mice, Knockout,
pubmed-meshheading:11867568-Mice, Transgenic,
pubmed-meshheading:11867568-Mutation,
pubmed-meshheading:11867568-Proteins,
pubmed-meshheading:11867568-Signal Transduction,
pubmed-meshheading:11867568-TNF Receptor-Associated Factor 2,
pubmed-meshheading:11867568-TNF Receptor-Associated Factor 3,
pubmed-meshheading:11867568-TNF Receptor-Associated Factor 5
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pubmed:year |
2002
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pubmed:articleTitle |
Dissection of B cell differentiation during primary immune responses in mice with altered CD40 signals.
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pubmed:affiliation |
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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