Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
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Pages (from-to) | 88 - 99 |
Journal | Immunity |
Volume | 2008 |
Issue number | 28 |
Publication status | Published - Jan 2008 |
Peer-reviewed | Yes |
Externally published | Yes |
External IDs
Scopus | 37849000098 |
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ORCID | /0000-0002-5381-0547/work/147141642 |