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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Eloisa Arana - , Cancer Research UK (Joint first author)
  • Anne Vehlow - , Cancer Research UK (Joint first author)
  • Naomi E. Harwood - , Cancer Research UK (Author)
  • Elena Vigorito - , Babraham Institute (Author)
  • Robert Henderson - , National Institute for Medical Research (NIMR) (Author)
  • Martin Turner - , Babraham Institute (Author)
  • Victor L. J. Tybulewicz - , National Institute for Medical Research (NIMR) (Author)
  • Facundo D. Batista - , Cancer Research UK (Last author)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)88 - 99
JournalImmunity
Volume2008
Issue number28
Publication statusPublished - Jan 2008
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 37849000098
ORCID /0000-0002-5381-0547/work/147141642

Keywords

Research priority areas of TU Dresden