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Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization

Immunoglobulin (Ig)α and Igβ initiate B cell receptor (BCR) signaling through immune receptor tyrosine activation motifs (ITAMs) that are targets of SH2 domain–containing kinases. To examine the function of Igβ ITAM tyrosine resides in mature B cells in vivo, we exchanged these residues for alanine...

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Detalles Bibliográficos
Autores principales: Gazumyan, Anna, Reichlin, Amy, Nussenzweig, Michel C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118343/
https://www.ncbi.nlm.nih.gov/pubmed/16818674
http://dx.doi.org/10.1084/jem.20060221
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author Gazumyan, Anna
Reichlin, Amy
Nussenzweig, Michel C.
author_facet Gazumyan, Anna
Reichlin, Amy
Nussenzweig, Michel C.
author_sort Gazumyan, Anna
collection PubMed
description Immunoglobulin (Ig)α and Igβ initiate B cell receptor (BCR) signaling through immune receptor tyrosine activation motifs (ITAMs) that are targets of SH2 domain–containing kinases. To examine the function of Igβ ITAM tyrosine resides in mature B cells in vivo, we exchanged these residues for alanine by gene targeting (Igβ(AA)). Mutant mice showed normal development of all B cell subtypes with the exception of B1 cells that were reduced by fivefold. However, primary B cells purified from Igβ(AA) mice showed significantly decreased steady-state and ligand-mediated BCR internalization and higher levels of cell surface IgM and IgD. BCR cross-linking resulted in decreased Src and Syk activation but paradoxically enhanced and prolonged BCR signaling, as measured by cellular tyrosine phosphorylation, Ca(++) flux, AKT, and ERK activation. In addition, B cells with the ITAM mutant receptor showed an enhanced response to a T-independent antigen. Thus, Igβ ITAM tyrosines help set BCR signaling threshold by regulating receptor internalization.
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spelling pubmed-21183432007-12-13 Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization Gazumyan, Anna Reichlin, Amy Nussenzweig, Michel C. J Exp Med Articles Immunoglobulin (Ig)α and Igβ initiate B cell receptor (BCR) signaling through immune receptor tyrosine activation motifs (ITAMs) that are targets of SH2 domain–containing kinases. To examine the function of Igβ ITAM tyrosine resides in mature B cells in vivo, we exchanged these residues for alanine by gene targeting (Igβ(AA)). Mutant mice showed normal development of all B cell subtypes with the exception of B1 cells that were reduced by fivefold. However, primary B cells purified from Igβ(AA) mice showed significantly decreased steady-state and ligand-mediated BCR internalization and higher levels of cell surface IgM and IgD. BCR cross-linking resulted in decreased Src and Syk activation but paradoxically enhanced and prolonged BCR signaling, as measured by cellular tyrosine phosphorylation, Ca(++) flux, AKT, and ERK activation. In addition, B cells with the ITAM mutant receptor showed an enhanced response to a T-independent antigen. Thus, Igβ ITAM tyrosines help set BCR signaling threshold by regulating receptor internalization. The Rockefeller University Press 2006-07-10 /pmc/articles/PMC2118343/ /pubmed/16818674 http://dx.doi.org/10.1084/jem.20060221 Text en Copyright © 2006, 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 Articles
Gazumyan, Anna
Reichlin, Amy
Nussenzweig, Michel C.
Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization
title Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization
title_full Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization
title_fullStr Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization
title_full_unstemmed Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization
title_short Igβ tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization
title_sort igβ tyrosine residues contribute to the control of b cell receptor signaling by regulating receptor internalization
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118343/
https://www.ncbi.nlm.nih.gov/pubmed/16818674
http://dx.doi.org/10.1084/jem.20060221
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