Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 24, Issue 13, Pages 5767-5775Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.24.13.5767-5775.2004
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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 Got subunits, likely fine tune the cellular responses to chemokines. Here we show that Rgs(-/-) 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 RgsI(-/-) 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.
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