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Abnormal B-Cell Responses to Chemokines, Disturbed Plasma Cell Localization, and Distorted Immune Tissue Architecture in Rgs1^–/– Mice

Chantal Moratz,^1, J. Russell Hayman,^3, Hua Gu,² and John H. Kehrl^1*

Laboratories of Immunoregulation,¹ Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,² Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614³

Received 22 December 2003/ Returned for modification 9 January 2004/ Accepted 24 March 2004

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 G 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.

C.M. and J.R.H. contributed equally to this work.

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