Inhibitory signaling by B cell FcγRIIb

The fact that B cells undergo feedback suppression, or negative signaling, through the interaction of secreted antibody with specific antigen has been extensively documented but the mechanisms involved in the process have been elusive. Experiments over the past year using B cell deletion mutants and dominant-negative enzymes have firmly established an important role for SH2-domain-containing inositol 5-phosphatase (SHIP) in negative signaling. Negative signaling through SHIP appears to inhibit the Ras pathway through SH2 domain competition with Grb2 and Shc and may involve consumption of intracellular lipid mediators that act as allosteric enzyme activators or that promote entry of extracellular Ca2+.