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

Chemokines bind receptors that are members of the G-protein-coupled receptor fam- ily. 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-ex- pressed in germinal center B cells and many Bur- kitt's lymphoma cell lines. Reducing RGS13 and to a lesser extent RGS1 expression in a Burkitt's lym- phoma 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 restimu- lation with CXCL12 or CXCL13 after a primary stimulation with CXCL12 than do the control cells. The double-KD cells also exhibit a greater propen- sity to polarize and to develop multiple small la- mellipodia. These results indicate that RGS1 and RGS13 act together to regulate chemokine recep- tor signaling in human germinal center B lympho- cytes and provide evidence that they contribute significantly to the rapid desensitization of the sig- naling pathway. J. Leukoc. Biol. 79: 1357-1368; 2006.