RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine ligand (CXCL)12 and CXCL13

Shi GX, Harrison K, Wilson GL, Moratz C and Kehrl JH
Source: J Immunol
Publication Date: (2002)
Issue: 169(5): 2507-2515
Research Area:
Immunotherapy / Hematology
Cells used in publication:
B cell, human
Species: human
Tissue Origin: blood
Nucleofectorâ„¢ I/II/2b
Normal lymphoid tissue development and function depend upon direct cell migration. RGS13 (regulator of G protein signaling) is involved in the G protein coupled signaling of chemokines to guide cell movement and positioning. To study the intracellular location of RGS13 the authors nucleofected mouse or human RGS13-GFP into primary human B cells and analyzed the transfected cells by confocal imaging. RGS13-GFP localized predominantly in the cytoplasm.
Normal lymphoid tissue development and function depend upon directed cell migration. Providing guideposts for cell movement and positioning within lymphoid tissues, chemokines signal through cell surface receptors that couple to heterotrimeric G proteins, which are in turn subject to regulation by regulator of G protein signaling (RGS) proteins. In this study, we report that germinal center B lymphocytes and thymic epithelial cells strongly express one of the RGS family members, RGS13. Located between Rgs1 and Rgs2, Rgs13 spans 42 kb on mouse chromosome 1. Rgs13 encodes a 157-aa protein that shares 82% amino acid identity with its 159-aa human counterpart. In situ hybridization with sense and antisense probes localized Rgs13 expression to the germinal center regions of mouse spleens and Peyer's patches and to the thymus medulla. Affinity-purified RGS13 Abs detected RGS13-expressing cells in the light zone of the germinal center. RGS13 interacted with both Gialpha and Gqalpha and strongly impaired signaling through G(i)-linked signaling pathways, including signaling through the chemokine receptors CXCR4 and CXCR5. Prolonged CD40 signaling up-regulated RGS13 expression in human tonsil B lymphocytes. These results plus previous studies of RGS1 indicate the germinal center B cells use two RGS proteins, RGS1 and RGS13, to regulate their responsiveness to chemokines.