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Molecular and Cellular Biology, July 2004, p. 5767-5775, Vol. 24, No. 13
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.13.5767-5775.2004

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

Chantal Moratz,1,{dagger} J. Russell Hayman,3,{dagger} Hua Gu,2 and John H. Kehrl1*

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{alpha} 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.


* Corresponding author. Mailing address: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 10, Room 11B08, 10 Center Dr., MSC 1876, Bethesda, MD 20892. Phone: (301) 402-4852. Fax: (301) 402-0070. E-mail: jkehrl{at}niaid.nih.gov.

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


Molecular and Cellular Biology, July 2004, p. 5767-5775, Vol. 24, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.13.5767-5775.2004




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