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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1993-3-24
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pubmed:abstractText |
Previous studies in our laboratory demonstrated that overnight exposure of adult splenic B cells to anti-Ig resulted in an unresponsive state characterized by decreased antibody synthesis but normal mitogen-driven proliferation (i.e., energy). Because both anti-F(ab')2 and anti-mu were equally effective at inducing tolerance, it was important to determine whether cross-linking of IgD together with or separately from IgM influenced the induction of unresponsiveness. Although anti-mu induced significant unresponsiveness, treatment of adult splenic B cells with anti-delta alone generally failed to reduce the subsequent response to either LPS or fluoresceinated Brucella abortus. Interestingly, anti-delta synergized with suboptimal concentrations of anti-mu to induce tolerance. Synergy could be observed in this system when anti-delta was added either simultaneously with or before (but not after) anti-mu; moreover, anti-delta was effective in a pretreatment (wash-out) protocol. To investigate the role of protein tyrosine kinase (PTK) activity in tolerance induction, splenic B cells were treated with tyrphostin before treatment with either anti-mu or anti-delta. We found that pretreatment with tyrphostin for 2 h before the addition of anti-mu prevented the induction of unresponsiveness with this antibody, whereas this PTK inhibitor facilitated tolerance when used with anti-delta treatment only. We propose that cross-linking of surface IgM directly or indirectly invokes a tyrphostin-sensitive, PTK-dependent pathway leading to the early events in tolerance induction, which can be augmented under limiting conditions by anti-IgD. Because cross-linking of either receptor initiates several common pathways, simultaneous cross-linking can lead to synergy and a dominance of the IgM signal. In contrast, IgD alone may fail to elicit tolerance because this isotype may also be associated with different PTK that cause positive signaling.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin D,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Isotypes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fc,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/immunoglobulin D receptor,
http://linkedlifedata.com/resource/pubmed/chemical/immunoglobulin M receptor
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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 |
150
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1663-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8436810-Animals,
pubmed-meshheading:8436810-Antibodies, Monoclonal,
pubmed-meshheading:8436810-B-Lymphocytes,
pubmed-meshheading:8436810-Immune Tolerance,
pubmed-meshheading:8436810-Immunoglobulin D,
pubmed-meshheading:8436810-Immunoglobulin Isotypes,
pubmed-meshheading:8436810-Immunoglobulin M,
pubmed-meshheading:8436810-Male,
pubmed-meshheading:8436810-Mice,
pubmed-meshheading:8436810-Mice, Inbred C57BL,
pubmed-meshheading:8436810-Mice, Inbred DBA,
pubmed-meshheading:8436810-Protein-Tyrosine Kinases,
pubmed-meshheading:8436810-Receptors, Antigen, B-Cell,
pubmed-meshheading:8436810-Receptors, Fc,
pubmed-meshheading:8436810-Receptors, Immunologic
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pubmed:year |
1993
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pubmed:articleTitle |
B cell tolerance induction by cross-linking of membrane IgM, but not IgD, and synergy by cross-linking of both isotypes.
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pubmed:affiliation |
Division of Immunology and Immunotherapy, University of Rochester Cancer Center, NY 14642.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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