RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine ligand (CXCL)12 and CXCL13.
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.
B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Geng-Xian
GX
Shi
Kathleen
K
Harrison
Gaye Lynn
GL
Wilson
Chantal
C
Moratz
John H
JH
Kehrl
D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016466:CHO Cells; D019556:COS Cells; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000502:physiology*; D002874:Chromosome Mapping; D006224:Cricetinae; D018076:DNA, Complementary / Q000032:analysis; D005786:Gene Expression Regulation / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D049452:Green Fluorescent Proteins; D018922:HL-60 Cells; D006367:HeLa Cells; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D020014:K562 Cells; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020710:RGS Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism
C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C486386:Cxcl13 protein, mouse; D018076:DNA, Complementary; D005819:Genetic Markers; D008164:Luminescent Proteins; D020710:RGS Proteins; C456322:RGS13 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020962:Heterotrimeric GTP-Binding Proteins