Lymphocyte Activation

Caspase activity is required for stimulated B lymphocytes to enter the cell cycle. Olson, N. R. et al. J. Immunol. 170, 6065–6072 (2003)

Caspases are best known for their role in apoptosis, but they have also been implicated in the regulation of cell proliferation. In particular, caspase-8 — the factor that is at the top of the proteolytic caspase cascade — has a role in T-cell proliferation, but the specific caspases that are involved downstream are unknown. This new study shows that caspase-8 and caspase-6 are essential for human B-cell proliferation. Inhibition of caspase-6 blocked the upregulation of expression of the cell-cycle regulators D-type cyclins and cyclin-dependent kinase 4 by activated B cells, indicating a possible mechanism, by which caspase-6 could regulate cell-cycle entry. Notably, other aspects of B-cell activation, such as cytokine secretion, were unaffected, indicating a specific role for caspase-6 in proliferation.

Lymphocyte Activation

The B cell-specific major raft protein, Raftlin, is necessary for the integrity of lipid raft and BCR signal transduction. Saeki, K. et al. EMBO J. 22, 3015–3026 (2003)

Membrane lipid microdomains known as rafts, which are rich in signalling molecules, have been proposed to have a crucial role in lymphocyte signalling. This study describes a new component of rafts in B cells, which has no homology to any other known protein and has been named Raftlin (for raft-linking protein). This molecule seems to localize in rafts by means of an acylated motif and is constitutively associated with the B-cell receptor (BCR), although it does not bind the BCR directly. In the absence of Raftlin, BCR signalling was impaired and levels of other key raft components, such as the tyrosine kinase LYN and ganglioside GM1, were markedly reduced, indicating that Raftlin is important for raft integrity.

Mucosal Immunology

Mast cells disrupt epithelial barrier function during enteric nematode infection. McDermott, J. R. et al. Proc. Natl Acad. Sci. USA 100, 7761–7766 (2003)

Expulsion of nematode parasites is associated with elevated epithelial permeability. Mast cells are also important for parasite expulsion, but the mechanism is not well understood. In this study, McDermott and colleagues show that mast cells are responsible for inducing the increased intestinal permeability, which seems to depend on degradation of the tight-junction protein occludin. The authors used c-Kit-specific antibodies to block mast-cell accumulation, which prevented parasite expulsion and correlated with less permeability than in control animals. Mice overexpressing interleukin-9, which have higher numbers of mast cells than normal mice, showed enhanced intestinal permeability and could get rid of the parasites faster.