B cell antigen receptor engagement inhibits stromal cell-derived factor (SDF)-1α chemotaxis and promotes protein kinase C (PKC)-induced internalization of CXCR4
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作者:
Guinamard, R
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机构:Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
Guinamard, R
Signoret, N
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机构:Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
Signoret, N
Masamichi, I
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机构:Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
Masamichi, I
Marsh, M
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机构:Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
Marsh, M
Kurosaki, T
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机构:Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
Kurosaki, T
Ravetch, JV
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机构:Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
Ravetch, JV
机构:
[1] Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
[2] UCL, Dept Biochem, London WC1E 6BT, England
[3] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England
[4] Kansai Med Univ, Dept Mol Genet, Moriguchi, Osaka 570, Japan
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)-1 alpha 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-1 alpha chemotaxis was dependent on Syk, BLNK, Btk, and phospholipase C (Plc)gamma 2 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-1 alpha 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-1 alpha migration is through PKC-dependent downregulation of CXCR4.
机构:
STANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USASTANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA
CYSTER, JG
HARTLEY, SB
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STANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USASTANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA
HARTLEY, SB
GOODNOW, CC
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STANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USASTANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA
机构:
UNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA
Goodnow, CC
Cyster, JG
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UNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA
机构:
STANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USASTANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA
CYSTER, JG
HARTLEY, SB
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STANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USASTANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA
HARTLEY, SB
GOODNOW, CC
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STANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USASTANFORD UNIV, BECKMAN CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA
机构:
UNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA
Goodnow, CC
Cyster, JG
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UNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA