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Caltech biologists discover how T cells make a commitment
Date:7/2/2010

hey are at that moment is what they are forever," Rothenberg says. Once T cells mature, their abilities to keep dividing and migrating around the body also give them the opportunity to have their daughters adopt different roles in the immune system as they encounter and interact with other types of cells. "Even so, their central T-cell nature remains unchanged, which means that they must have a strong sense of identity," she adds.

The conversion from T-cell precursors to actual T cells takes place in the thymus, a specialized organ located near the heart. "When the future T cells move into the thymus," Rothenberg explains, "they are expressing a variety of genes that give them the option to become other cells," such as mast cells (which are involved in allergic reactions), killer cells (which kill cells infected by viruses), and antigen-presenting cells (which help T cells recognize targeted foreign cells).

As they enter the thymus, the organ sends molecular signals to the cells, directing them down the T-cell pathway. At this point, the Rothenberg lab found, the Bcl11b gene gets turned on. Li, the lead author on the Science paper, found that this confirms the T cells' identity by blocking other pathways. The Bcl11b protein is also needed for the cells to make the break from their stem-cell heritage. "It is like a switch that allows the cells to shut off stem-cell genes and other regulatory genes," Rothenberg says. "It keeps them cleanand may be necessary to 'guard' the T cell from becoming some other type of cell."

Although it is thought that many genes are involved in the process of creating and maintaining T cells, "Bcl11b is the only regulatory gene in the whole genome to be turned on at this stage," she adds, "and it is probably always active in all T cells. It is the most T-cell specific of all of the regulatory factors discovered so far." Among blood cells, this gene is only expressed in T cells, she says. "The gene is used in o
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Contact: Kathy Svitil
ksvitil@caltech.edu
626-395-8022
California Institute of Technology
Source:Eurekalert

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