The Journal of Experimental Medicine
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Published online 17 April 2000.
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© The Rockefeller University Press, 0022-1007/2000/4/1443/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 8, April 17, 2000 1443-1448

Brief Definitive Report

Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells

Bennett C. Weintrauba, Jesse Eunsuk Juna, Anthony C. Bishopb, Kevan M. Shokatb, Matthew L. Thomasc, and Christopher C. Goodnowa

a Australian Cancer Research Foundation Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Canberra 2601, Australia
b Department of Chemistry, Princeton University, Princeton, New Jersey 08544
c Howard Hughes Medical Institute and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110
Medical Genome Centre, John Curtin School of Medical Research, ANU, Mills Rd., Canberra 2601 ACT, Australia.61-2-6279-851261-2-6249-3621

Chris.Goodnow{at}anu.edu.au

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.

Key Words: B cell antigen receptor signaling • tyrosine phosphorylation • membrane raft • self-tolerance • anergy

© 2000 The Rockefeller University Press


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