RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization

J Leukoc Biol. 2006 Jun;79(6):1357-68. doi: 10.1189/jlb.1105693. Epub 2006 Mar 24.

Abstract

Chemokines bind receptors that are members of the G-protein-coupled receptor family. Chemokine receptors transduce intracellular signals by activating heterotrimeric G-proteins. Acting to limit and modulate heterotrimeric G-protein signaling is a family of proteins, termed regulator of G-protein signaling (RGS). Two of these proteins, RGS1 and RGS13, are well-expressed in germinal center B cells and many Burkitt's lymphoma cell lines. Reducing RGS13 and to a lesser extent RGS1 expression in a Burkitt's lymphoma cell line enhances responsiveness to two chemokines, CXC chemokine ligand 12 (CXCL12) and CXCL13, and reducing both mRNAs augments the responses more dramatically. The double knock-down (KD) cells respond better to restimulation with CXCL12 or CXCL13 after a primary stimulation with CXCL12 than do the control cells. The double-KD cells also exhibit a greater propensity to polarize and to develop multiple small lamellipodia. These results indicate that RGS1 and RGS13 act together to regulate chemokine receptor signaling in human germinal center B lymphocytes and provide evidence that they contribute significantly to the rapid desensitization of the signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / physiology
  • Burkitt Lymphoma / pathology
  • Cell Line, Tumor / drug effects
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology
  • Chemotaxis / drug effects*
  • Genetic Vectors / genetics
  • Germinal Center / cytology*
  • Humans
  • Lentivirus / genetics
  • Platelet Activating Factor / pharmacology
  • RGS Proteins / genetics
  • RGS Proteins / physiology*
  • RNA Interference*
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Platelet Activating Factor
  • RGS Proteins
  • RGS1 protein, human
  • RGS13 protein, human
  • RNA, Messenger
  • Recombinant Fusion Proteins