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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0001675,
umls-concept:C0004561,
umls-concept:C0021289,
umls-concept:C0026809,
umls-concept:C0037083,
umls-concept:C0037993,
umls-concept:C0205252,
umls-concept:C0591833,
umls-concept:C0851285,
umls-concept:C1167322,
umls-concept:C1705241,
umls-concept:C1705242,
umls-concept:C1710082,
umls-concept:C2752508,
umls-concept:C2754998
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pubmed:issue |
5
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pubmed:dateCreated |
1991-3-19
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pubmed:abstractText |
During the course of B lymphocyte development, newly emerging surface Ig+ B cells pass through a stage when Ag-Ag receptor interactions lead not to immune responsiveness but to a state of functional tolerance. We have explored the molecular basis of antigenic nonresponsiveness and tolerance susceptibility using tolerance-susceptible surface Ig+ splenic B lymphocytes from neonatal mice and anti-mu chain antibodies as a polyclonal ligand. In this population of cells, surface IgM is uncoupled from the inositol phospholipid (PI)-hydrolysis pathway at a point proximal to the receptor; anti-mu antibodies did not stimulate inositol phosphate generation despite the fact that PI-hydrolysis was observed after treatment with A1F4, implicating the existence of a functional G protein and phospholipase C. Further evidence for a difference early in the signal transduction pathway stems from the finding that anti-mu stimulation does not induce the expression of two immediate/early PKC-linked genes egr-1 and c-fos. This appears to be the primary signaling difference between the mature and immature B cells from the neonatal mouse splenic population, as these cells undergo a G0-G1 cell cycle phase transition when surface IgM is bypassed using phorbol diester and calcium ionophore. Interestingly, despite undetectable levels of PI-hydrolysis, we observed equivalent receptor-mediated changes in intracellular calcium when comparing the immature and mature populations. These results indicate incomplete coupling of surface IgM to the signal transduction machinery operative in mature, immunocompetent B cells and suggests a molecular mechanism accounting for the differential processing of surface IgM signals into activation vs tolerogenic responses observed in these two stages of B cell development.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/Ionomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
146
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1446-54
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1847161-Aging,
pubmed-meshheading:1847161-Animals,
pubmed-meshheading:1847161-Animals, Newborn,
pubmed-meshheading:1847161-B-Lymphocytes,
pubmed-meshheading:1847161-Calcium,
pubmed-meshheading:1847161-Cell Cycle,
pubmed-meshheading:1847161-Cross-Linking Reagents,
pubmed-meshheading:1847161-Immune Tolerance,
pubmed-meshheading:1847161-Immunoglobulin M,
pubmed-meshheading:1847161-Ionomycin,
pubmed-meshheading:1847161-Lymphocyte Activation,
pubmed-meshheading:1847161-Mice,
pubmed-meshheading:1847161-Mice, Inbred BALB C,
pubmed-meshheading:1847161-Phosphatidylinositols,
pubmed-meshheading:1847161-Receptors, Antigen, B-Cell,
pubmed-meshheading:1847161-Signal Transduction,
pubmed-meshheading:1847161-Spleen,
pubmed-meshheading:1847161-Tetradecanoylphorbol Acetate
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pubmed:year |
1991
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pubmed:articleTitle |
Signaling through surface IgM in tolerance-susceptible immature murine B lymphocytes. Developmentally regulated differences in transmembrane signaling in splenic B cells from adult and neonatal mice.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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