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B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4

The entry of B lymphocytes into secondary lymphoid organs is a critical step in the development of an immune response, providing a site for repertoire shaping, antigen-induced activation and selection. These events are controlled by signals generated through the B cell antigen receptor (BCR) and are...

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Autores principales: Guinamard, Rodolphe, Signoret, Nathalie, Ishiai, Masamichi, Marsh, Mark, Kurosaki, Tomohiro, Ravetch, Jeffrey V.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193069/
https://www.ncbi.nlm.nih.gov/pubmed/10224286
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author Guinamard, Rodolphe
Signoret, Nathalie
Ishiai, Masamichi
Marsh, Mark
Kurosaki, Tomohiro
Ravetch, Jeffrey V.
author_facet Guinamard, Rodolphe
Signoret, Nathalie
Ishiai, Masamichi
Marsh, Mark
Kurosaki, Tomohiro
Ravetch, Jeffrey V.
author_sort Guinamard, Rodolphe
collection PubMed
description The entry of B lymphocytes into secondary lymphoid organs is a critical step in the development of an immune response, providing a site for repertoire shaping, antigen-induced activation and selection. These events are controlled by signals generated through the B cell antigen receptor (BCR) and are associated with changes in the migration properties of B cells in response to chemokine gradients. The chemokine stromal cell–derived factor (SDF)-1α is thought to be one of the driving forces during those processes, as it is produced inside secondary lymphoid organs and induces B lymphocyte migration that arrests upon BCR engagement. The signaling pathway that mediates this arrest was genetically dissected using B cells deficient in specific BCR-coupled signaling components. BCR-induced inhibition of SDF-1α chemotaxis was dependent on Syk, BLNK, Btk, and phospholipase C (Plc)γ2 but independent of Ca(2+) mobilization, suggesting that the target of BCR stimulation was a protein kinase C (PKC)-dependent substrate. This target was identified as the SDF-1α receptor, CXCR4, which undergoes PKC- dependent internalization upon BCR stimulation. Mutation of the internalization motif SSXXIL in the COOH terminus of CXCR4 resulted in B cells that constitutively expressed this receptor upon BCR engagement. These studies suggest that one pathway by which BCR stimulation results in inhibition of SDF-1α migration is through PKC-dependent downregulation of CXCR4.
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spelling pubmed-21930692008-04-16 B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4 Guinamard, Rodolphe Signoret, Nathalie Ishiai, Masamichi Marsh, Mark Kurosaki, Tomohiro Ravetch, Jeffrey V. J Exp Med Articles The entry of B lymphocytes into secondary lymphoid organs is a critical step in the development of an immune response, providing a site for repertoire shaping, antigen-induced activation and selection. These events are controlled by signals generated through the B cell antigen receptor (BCR) and are associated with changes in the migration properties of B cells in response to chemokine gradients. The chemokine stromal cell–derived factor (SDF)-1α is thought to be one of the driving forces during those processes, as it is produced inside secondary lymphoid organs and induces B lymphocyte migration that arrests upon BCR engagement. The signaling pathway that mediates this arrest was genetically dissected using B cells deficient in specific BCR-coupled signaling components. BCR-induced inhibition of SDF-1α chemotaxis was dependent on Syk, BLNK, Btk, and phospholipase C (Plc)γ2 but independent of Ca(2+) mobilization, suggesting that the target of BCR stimulation was a protein kinase C (PKC)-dependent substrate. This target was identified as the SDF-1α receptor, CXCR4, which undergoes PKC- dependent internalization upon BCR stimulation. Mutation of the internalization motif SSXXIL in the COOH terminus of CXCR4 resulted in B cells that constitutively expressed this receptor upon BCR engagement. These studies suggest that one pathway by which BCR stimulation results in inhibition of SDF-1α migration is through PKC-dependent downregulation of CXCR4. The Rockefeller University Press 1999-05-03 /pmc/articles/PMC2193069/ /pubmed/10224286 Text en 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
Guinamard, Rodolphe
Signoret, Nathalie
Ishiai, Masamichi
Marsh, Mark
Kurosaki, Tomohiro
Ravetch, Jeffrey V.
B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4
title B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4
title_full B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4
title_fullStr B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4
title_full_unstemmed B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4
title_short B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4
title_sort b cell antigen receptor engagement inhibits stromal cell–derived factor (sdf)-1α chemotaxis and promotes protein kinase c (pkc)-induced internalization of cxcr4
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193069/
https://www.ncbi.nlm.nih.gov/pubmed/10224286
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