Regulation of integrin activation through the B-cell receptor

ELOISA ARANA; ANNE VEHLOW; FACUNDO D. BATISTA

Congreso; Sociedad Argntina de Inmunología; 2009

Membrane-displayed antigens are specially effective at triggering B cell activation and may constitute the dominant form of antigen responsible for B cell stimulation in vivo. B cell encounter with specific membrane-antigens promotes cell adhesion and concomitant formation of an immune synapse (IS). We followed a genetic approach to investigate the molecular mechanism that underlies the antigen-induced cytoskeleton reorganisation and subsequent activation of LFA-1-mediated B-cell adhesion, and found that the process of ?inside-out? activation of LFA-1 required the activation of Src-family kinases and phosphoinositide 3-kinase (PI3K). In addition, LFA-1-mediated B-cell adhesion also requires the guanine nucleotide-exchange factors (GEFs) Vav1 and Vav2. Surprisingly, we found that Rac2, but not the highly homologous Rac1, is necessary for activation of LFA-1-mediated B-cell adhesion. Moreover, in the absence of Rac2, but not Rac1, the levels of Rap1-GTP were compromised and there were severe actin polymerisation defects, suggesting a mechanism by which Rac2 mediates its cellular effects. Our results shed light on a novel pathway for activation of LFA-1 and highlight the interplay between signalling and cytoskeletal remodelling that drives membrane-antigen recognition