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New tool reveals secrets of migrating cells

suggest that this exploration probably is a search for a signal that will decide the cell's fate. In their experiments on one lobe of the mouse thymus, in fact, Witt and her colleagues saw cells, possibly those that have made a decision on their fate, halt their wanderings and make a beeline out of the cortex to the medulla, something immature T cells can't do.

The scenario they've reconstructed from the video and mathematical analysis starts with immature T cells moving out of the center of the thymus, the medulla, to the very outside edge of the cortex, where they proliferate and fill up the cortex. At this point, Witt said, they undergo the first of two tests to see if their surface receptors (called T cell receptors) work properly.

Once they pass that test, they start wandering around in the cortex looking for the second test, which is to bind precisely to a protein called the major histocompatibility complex (MHC). These cells, the researchers think, are the meanderers. Only about one percent of thymocytes pass both tests, but Witt and Robey think that those that do are the ones they see beelining out of the cortex into the medulla to begin their two-week education to distinguish "self" from "non-self" invader.

"To pass into the medulla they have to pass a screening test called positive selection," Witt said. "Once they do, the cells move very directly at a very fast speed inward toward the medulla, adopting a polarized shape characteristic of migrating cells."

While Witt and Robey continue their two-photon imaging studies of thymus cells and lymph cells, Witt is trying to encourage the technology's use in biology generally.

"Immunology is just one example of a subdiscipline of biology that stands to benefit enormously from our new ability to see in four-dimensions - in 3-D in real time. It opens an entirely different universe to us," Witt said.

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Source:University of California - Berkeley


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