Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation.
The integrin leukocyte function-associated antigen-1 (LFA-1) is important in the promotion of B cell adhesion, thereby facilitating immunological synapse (IS) formation and B cell activation. Despite this significance, the associated signaling mechanisms regulating LFA-1 activation remain elusive. Here, we show that both isoforms of the small GTPase Rac expressed by primary B cells, Rac1 and Rac2, were activated rapidly downstream of Src-family kinases, guanine-nucleotide exchange factors Vav1 and Vav2, and phosphoinositide-3 kinase (PI3K) after BCR engagement. We identify Rac2, but not Rac1, as critical for B cell adhesion to intercellular adhesion molecule-1 (ICAM-1) and IS formation. Furthermore, B cells expressing constitutively active Rac2 are highly adhesive. We observe that Rac2-deficient B cells exhibit lower amounts of Rap1-GTP and severe actin polymerization defects, identifying a potential mechanism underlying their behavior. We postulate that this critical role for Rac2 in mediating B cell adhesion and IS formation might apply in all lymphocytes.
Arana
Eloisa
E
Lymphocyte Interaction Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Vehlow
Anne
A
Harwood
Naomi E
NE
Vigorito
Elena
E
Henderson
Robert
R
Turner
Martin
M
Tybulewicz
Victor L J
VL
Batista
Facundo D
FD
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology*; D004789:Enzyme Activation / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009479:Neuropeptides / Q000276:immunology / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection; D020744:rac GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein; D019061:src-Family Kinases / Q000276:immunology / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
D018799:Intercellular Adhesion Molecule-1; D009479:Neuropeptides; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D019061:src-Family Kinases; D000097766:RAC2 GTP-Binding Protein; C484602:Rac1 protein, mouse; C496619:Vav1 protein, mouse; C490565:Vav2 protein, mouse