Stimulating T cells boosts ROS production (top row), but not if Bak and Bax are absent (bottom row).


Two cell-killing proteins also have a nurturing side, say Russell Jones, Craig Thompson (University of Pennsylvania, Philadelphia, PA), and colleagues. Although the proteins prod lymphocytes to commit suicide, they also prompt the cells to proliferate—and might do the same for a variety of cell types.

The two proteins, Bax and Bak, are part of the apoptotic machinery in T lymphocytes. Weeding out excess T cells turns down the immune response after a pathogen has been defeated. Mice that lack Bax and Bak in blood cells often fall victim to infections, suggesting that the two proteins are also involved in lymphocyte activation.

The researchers found that T cells missing Bak and Bax divided slowly after stimulation. Injecting bacteria into mice lacking both proteins in their lymphocytes didn't provoke a T cell response to the invaders. T cell activation involves a surge in intracellular calcium, but loss of Bax and Bak reduced this increase. The scientists discovered that rising calcium levels boosted production of reactive oxygen species (ROS) in the cell, which is essential for proliferation.

The work suggests that Bax and Bak rouse T cells in part by hiking ROS levels. These compounds can also kill cells, and the mechanism for adjusting ROS quantities to favor death or division remains uncertain. But Bax and Bak might regulate ROS production to awaken other quiescent cells, such as stem cells.


Jones, R.G., et al.