Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles.
Signaling by G protein-coupled receptors coupled to Galpha(i) assists in triggering lymphocyte movement into and out of lymph nodes. Here, we show that modulating the signaling output from these receptors dramatically alters B cell trafficking. Intravital microscopy of adoptively transferred B cells from wild-type and Rgs1-/- mice revealed that Rgs1-/- B cells stick better to lymph node high endothelial venules, home better to lymph nodes, and move more rapidly within lymph node follicles than do wild-type B cells. In contrast, B cells from Gnai2-/- mice enter lymph nodes poorly and move more slowly than do wild-type B cells. The Gnai2-/- mice often lack multiple peripheral lymph nodes, and their B cells respond poorly to chemokines, indicating that Galpha(i1) and Galpha(i3) poorly compensate for the loss of Galpha(i2). These results demonstrate opposing roles for Rgs1 and Gnai2 in B cell trafficking into and within lymph nodes.
Han
Sang-Bae
SB
Laboratory of Immunoregulation, National Institute of Allergy and Infectious, Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Moratz
Chantal
C
Huang
Ning-Na
NN
Kelsall
Brian
B
Cho
Hyeseon
H
Shi
Chong-Shan
CS
Schwartz
Owen
O
Kehrl
John H
JH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000276:immunology*; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D020710:RGS Proteins / Q000276:immunology*
D011518:Proto-Oncogene Proteins; D020710:RGS Proteins; C488188:Rgs1 protein, mouse; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse