Dissection of the signalling mechanisms underlying FcgammaRIIB-mediated apoptosis of mature B-cells.

The low-affinity receptor for IgG, FcgammaRIIB, negatively regulates BCR (B-cell antigen receptor)-mediated proliferative signalling and thus plays an important role in feedback inhibition of the humoral immune response. Whereas crosslinking of BCR on mature B-cells results in proliferation, co-ligation of FcgammaRIIB results in growth arrest and apoptosis. We have now investigated the signals underlying FcgammaRIIB-driven apoptosis and found this to be dependent on disruption of mitochondrial potential (Deltapsi), involve the pro-apoptotic Bcl-2 family members, Bid and Bad, and be caspase-independent.