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Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk

During B lymphoid ontogeny, assembly of the pre–B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Bl...

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Autores principales: Tretter, Theresa, Ross, Ashley E., Dordai, Dominic I., Desiderio, Stephen
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194155/
https://www.ncbi.nlm.nih.gov/pubmed/14662906
http://dx.doi.org/10.1084/jem.20030729
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author Tretter, Theresa
Ross, Ashley E.
Dordai, Dominic I.
Desiderio, Stephen
author_facet Tretter, Theresa
Ross, Ashley E.
Dordai, Dominic I.
Desiderio, Stephen
author_sort Tretter, Theresa
collection PubMed
description During B lymphoid ontogeny, assembly of the pre–B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7. In mice lacking a functional pre-BCR, active Blk supported maturation beyond the pro–B cell stage, suppressed V(H) to DJ(H) rearrangement, relieved selection for productive heavy chain rearrangement, and stimulated κ rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin β and Syk, as well as changes in gene expression consistent with developmental maturation. Thus, sustained activation of Blk induces responses normally associated with the pre-BCR.
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spelling pubmed-21941552008-04-11 Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk Tretter, Theresa Ross, Ashley E. Dordai, Dominic I. Desiderio, Stephen J Exp Med Article During B lymphoid ontogeny, assembly of the pre–B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7. In mice lacking a functional pre-BCR, active Blk supported maturation beyond the pro–B cell stage, suppressed V(H) to DJ(H) rearrangement, relieved selection for productive heavy chain rearrangement, and stimulated κ rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin β and Syk, as well as changes in gene expression consistent with developmental maturation. Thus, sustained activation of Blk induces responses normally associated with the pre-BCR. The Rockefeller University Press 2003-12-15 /pmc/articles/PMC2194155/ /pubmed/14662906 http://dx.doi.org/10.1084/jem.20030729 Text en Copyright © 2003, 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 Article
Tretter, Theresa
Ross, Ashley E.
Dordai, Dominic I.
Desiderio, Stephen
Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk
title Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk
title_full Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk
title_fullStr Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk
title_full_unstemmed Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk
title_short Mimicry of Pre–B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk
title_sort mimicry of pre–b cell receptor signaling by activation of the tyrosine kinase blk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194155/
https://www.ncbi.nlm.nih.gov/pubmed/14662906
http://dx.doi.org/10.1084/jem.20030729
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