title: G12/G13 family G proteins regulate marginal zone B cell maturation, migration, and polarization.
abstract: 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 G(i) 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 alpha-subunits G alpha12 and G alpha13 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 G alpha12/G alpha13-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.
authors.affiliation: Institute of Pharmacology, University of Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rieken
authors.forename: Antonia
authors.initials: A
authors.lastname: Sassmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Herroeder
authors.forename: Barbara
authors.initials: B
authors.lastname: Wallenwein
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moers
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.forename: Nina
authors.initials: N
authors.lastname: Wettschureck
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D044365:GTP-Binding Protein alpha Subunits, G12-G13