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Related Experiment Videos

Differences in CXCR4-mediated signaling in B cells.

Elena Palmesino1, Barbara Moepps, Peter Gierschik

  • 1Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.

Immunobiology
|May 24, 2006
PubMed
Summary

Chemokine receptor CXCR4 signaling capacity changes during B cell development. While early B cells respond to CXCL12 with calcium mobilization, mature B cells exhibit altered pathways, suggesting a role for accessory proteins.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Chemokine receptor CXCR4 has a unique, prolonged signaling capacity.
  • CXCR4 is continuously expressed on B cells throughout lymphopoiesis.

Purpose of the Study:

  • Investigate CXCR4 signaling to its ligand CXCL12 in B cell lines and primary B lymphocytes.
  • Determine how CXCR4 signaling changes during B cell development.

Main Methods:

  • Stimulation of B cells with CXCL12.
  • Analysis of intracellular calcium mobilization.
  • Activation of small GTPases Rac1 and Cdc42.
  • MAP-kinase cascade activation assays.
  • Pertussis toxin and PI3-kinase inhibition assays.

Main Results:

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  • PreB and proB cells migrate towards CXCL12, mobilize calcium, and activate Rac1/Cdc42.
  • Mature B cells do not show these initial responses but retain migration to CXCL13 and CCL21.
  • CXCL12 stimulation at all B cell stages causes MAP-kinase cascade activation and CXCR4 internalization.
  • ERK1/2 activation pathways differ between preB and mature B cells, with PI3-kinase inhibition affecting mature B cells.

Conclusions:

  • CXCR4 coupling to downstream signal-transduction pathways is altered during B cell development.
  • Receptor activity may be modulated by accessory proteins in B cells.