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* Institute of Pharmacology and
Institute of Anesthesiology, University of Heidelberg, Heidelberg, Germany
G protein-coupled receptors play an important role in the regulation of lymphocyte functions such as migration, adhesion, proliferation, and differentiation. Although the role of Gi family G proteins has been intensively studied, no in vivo data exist with respect to G12/G13 family G proteins. We show in this study that mice that lack the G protein 
-subunits G12 and G13 selectively in B cells show significantly reduced numbers of splenic marginal zone B (MZB) cells, resulting in a delay of Ab production in response to thymus-independent Ags. Basal and chemokine-induced adhesion to ICAM-1 and VCAM-1, two adhesion molecules critically involved in MZB localization, is normal in mutant B cells, and the same is true for chemokine-induced migration. However, migration in response to serum and sphingosine 1-phosphate is strongly increased in mutant MZB cells, but not in mutant follicular B cells. Live-cell imaging studies revealed that G12/G13-deficient MZB cells assumed more frequently an ameboid form than wild-type cells, and pseudopod formation was enhanced. In addition to their regulatory role in serum- and sphingosine 1-phosphate-induced migration, G12/G13 family G proteins seem to be involved in peripheral MZB cell maturation, because also splenic MZB cell precursors are reduced in mutant mice, although less prominently than mature MZB cells. These data suggest that G12/G13 family G proteins contribute to the formation of the mature MZB cell compartment both by controlling MZB cell migration and by regulating MZB cell precursor maturation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Collaborative Research Center 405 of the Deutsche Forschungsgemeinschaft.
2 Address correspondence and reprint requests to Dr. Nina Wettschureck, Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany. E-mail address: Nina.Wettschureck{at}pharma.uni-heidelberg.de
3 Abbreviations used in this paper: RhoGEF, Rho guanine nucleotide exchange factor; MZB, marginal zone B; int, intermediate; S1P, sphingosine 1-phosphate; LPA, lysophosphatidic acid; DKO, double knockout; WT, wild type; MAdCAM-1, mucosal addressin cell adhesion molecule-1; MARCO, macrophage receptor with collagenous structure; TNP, trinitrophenyl; HSA, heat-stable Ag.
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