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 Ca2+ 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.
Skip Nav Destination
Article navigation
3 May 1999
Article|
May 03 1999
B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4
Rodolphe Guinamard,
Rodolphe Guinamard
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Search for other works by this author on:
Nathalie Signoret,
Nathalie Signoret
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Search for other works by this author on:
Masamichi Ishiai,
Masamichi Ishiai
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Search for other works by this author on:
Mark Marsh,
Mark Marsh
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Search for other works by this author on:
Tomohiro Kurosaki,
Tomohiro Kurosaki
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Search for other works by this author on:
Jeffrey V. Ravetch
Jeffrey V. Ravetch
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Search for other works by this author on:
Rodolphe Guinamard
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Nathalie Signoret
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Masamichi Ishiai
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Mark Marsh
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Tomohiro Kurosaki
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Jeffrey V. Ravetch
From the *Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the ‡Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom; and the §Department of Molecular Genetics, Kansai Medical University, Moriguchi, Osaka 570, Japan
Address correspondence to Jeffrey V. Ravetch, Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: 212-327-7321; Fax: 212-327-7319; E-mail: [email protected]
Received:
February 18 1999
Revision Received:
March 15 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (9): 1461–1466.
Article history
Received:
February 18 1999
Revision Received:
March 15 1999
Connected Content
This article has been corrected
Correction
Citation
Rodolphe Guinamard, Nathalie Signoret, Masamichi Ishiai, Mark Marsh, Tomohiro Kurosaki, Jeffrey V. Ravetch; B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4 . J Exp Med 3 May 1999; 189 (9): 1461–1466. doi: https://doi.org/10.1084/jem.189.9.1461
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Connected Content
Advertisement
