Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling in autoreactive B cells, a transgenic model was used to isolate a homogeneous population of tolerant B lymphocytes. These cells were compared with a similar population of naive B lymphocytes. We show that the BCR from naive B cells enters a detergent-insoluble domain of the cell within 6 s after antigen binding, before a detectable increase in BCR phosphorylation. This fraction appears to be important for signaling because it is enriched for lyn kinase but lacks CD45 tyrosine phosphatase and because the BCR that moves into this domain becomes more highly phosphorylated. Partitioning of the BCR into this fraction is unaffected by src family kinase inhibition. Tolerant B cells do not efficiently partition the BCR into the detergent-insoluble domain, providing an explanation for their reduced tyrosine kinase activation and calcium flux in response to antigen. These results identify an early, regulated step in antigen receptor signaling and self-tolerance.
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17 April 2000
Brief Definitive Report|
April 18 2000
Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
Bennett C. Weintraub,
Bennett C. Weintraub
aAustralian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Canberra 2601, Australia
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Jesse Eunsuk Jun,
Jesse Eunsuk Jun
aAustralian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Canberra 2601, Australia
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Anthony C. Bishop,
Anthony C. Bishop
bDepartment of Chemistry, Princeton University, Princeton, New Jersey 08544
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Kevan M. Shokat,
Kevan M. Shokat
bDepartment of Chemistry, Princeton University, Princeton, New Jersey 08544
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Matthew L. Thomas,
Matthew L. Thomas
cHoward Hughes Medical Institute and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110
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Christopher C. Goodnow
Christopher C. Goodnow
aAustralian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Canberra 2601, Australia
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Bennett C. Weintraub
aAustralian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Canberra 2601, Australia
Jesse Eunsuk Jun
aAustralian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Canberra 2601, Australia
Anthony C. Bishop
bDepartment of Chemistry, Princeton University, Princeton, New Jersey 08544
Kevan M. Shokat
bDepartment of Chemistry, Princeton University, Princeton, New Jersey 08544
Matthew L. Thomas
cHoward Hughes Medical Institute and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110
Christopher C. Goodnow
aAustralian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Canberra 2601, Australia
Received:
May 14 1999
Revision Requested:
December 28 1999
Accepted:
January 03 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (8): 1443–1448.
Article history
Received:
May 14 1999
Revision Requested:
December 28 1999
Accepted:
January 03 2000
Citation
Bennett C. Weintraub, Jesse Eunsuk Jun, Anthony C. Bishop, Kevan M. Shokat, Matthew L. Thomas, Christopher C. Goodnow; Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells. J Exp Med 17 April 2000; 191 (8): 1443–1448. doi: https://doi.org/10.1084/jem.191.8.1443
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