G12/G13 family G proteins regulate marginal zone B cell maturation, migration, and polarization.
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.
Rieken
Stefan
S
Institute of Pharmacology, University of Heidelberg, Germany.
Sassmann
Antonia
A
Herroeder
Susanne
S
Wallenwein
Barbara
B
Moers
Alexandra
A
Offermanns
Stefan
S
Wettschureck
Nina
N
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
D044365:GTP-Binding Protein alpha Subunits, G12-G13