Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation

ARANA, E.; VEHLOW, A.; HARWOOD, N. E.; VIGORITO, E.; HENDERSON, R; TURNER, M; TYBULEWICZ, V. L.; BATISTA, F. D

IMMUNITY

CELL PRESS

Año: 2008 vol. 28 p. 88 - 99

1074-7613

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 formationmight apply in all lymphocytes.