Abnormal B-cell responses to chemokines, disturbed plasma cell localization, and distorted immune tissue architecture in Rgs1-/- mice.
Normal lymphoid tissue development and function depend upon chemokine-directed cell migration. Since chemokines signal through heterotrimeric G-protein-coupled receptors, RGS proteins, which act as GTPase-activating proteins for Galpha subunits, likely fine tune the cellular responses to chemokines. Here we show that Rgs1(-/-) mice possess B cells that respond excessively and desensitize improperly to the chemokines CXCL12 and CXCL13. Many of the B-cell follicles in the spleens of Rgs1(-/-) mice have germinal centers even in the absence of immune stimulation. Furthermore, immunization of these mice leads to exaggerated germinal center formation; partial disruption of the normal architecture of the spleen and Peyer's patches; and abnormal trafficking of immunoglobulin-secreting cells. These results reveal the importance of a regulatory mechanism that limits and desensitizes chemokine receptor signaling.
Moratz
Chantal
C
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hayman
J Russell
JR
Gu
Hua
H
Kehrl
John H
JH
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D018925:Chemokines / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D018858:Germinal Center / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology*; D020710:RGS Proteins / Q000172:deficiency / Q000276:immunology* / Q000502:physiology; D013154:Spleen / Q000473:pathology
D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C486386:Cxcl13 protein, mouse; D020710:RGS Proteins; C488188:Rgs1 protein, mouse