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

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...

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Autores principales: Weintraub, Bennett C., Jun, Jesse Eunsuk, Bishop, Anthony C., Shokat, Kevan M., Thomas, Matthew L., Goodnow, Christopher C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193133/
https://www.ncbi.nlm.nih.gov/pubmed/10770810
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author Weintraub, Bennett C.
Jun, Jesse Eunsuk
Bishop, Anthony C.
Shokat, Kevan M.
Thomas, Matthew L.
Goodnow, Christopher C.
author_facet Weintraub, Bennett C.
Jun, Jesse Eunsuk
Bishop, Anthony C.
Shokat, Kevan M.
Thomas, Matthew L.
Goodnow, Christopher C.
author_sort Weintraub, Bennett C.
collection PubMed
description 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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spelling pubmed-21931332008-04-16 Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells Weintraub, Bennett C. Jun, Jesse Eunsuk Bishop, Anthony C. Shokat, Kevan M. Thomas, Matthew L. Goodnow, Christopher C. J Exp Med Brief Definitive Report 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. The Rockefeller University Press 2000-04-17 /pmc/articles/PMC2193133/ /pubmed/10770810 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Weintraub, Bennett C.
Jun, Jesse Eunsuk
Bishop, Anthony C.
Shokat, Kevan M.
Thomas, Matthew L.
Goodnow, Christopher C.
Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
title Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
title_full Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
title_fullStr Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
title_full_unstemmed Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
title_short Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
title_sort entry of b cell receptor into signaling domains is inhibited in tolerant b cells
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193133/
https://www.ncbi.nlm.nih.gov/pubmed/10770810
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