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Chemical attraction needed to launch an immune attack

A team led by UCSF scientists has determined how the weapons producers of the immune system - the B cells that make antibodies - find the T cells they must team up with to attack invading pathogens. The discovery may provide a strategy to block autoimmune diseases, the study's leaders suggests.

Chemical attraction is the key, the researchers found. Before they encounter foreign microbes, B cells concentrate in regions where few T cells reside, moored by their attraction to a certain kind of molecule called a chemokine. But contact with antigen from an invading microbe triggers changes in the B cell surface that draw them, irresistibly, to another type of chemokine, concentrated in T cell-rich sites.

This shifting balance of opposing chemical attractants may underlie a broad range of cellular movement in embryological development, the scientists conclude.

The research, based on studies of mice, is published in the March 7 issue of the journal Nature.

In their "nave" state, before they encounter antigen from potential pathogens, B cells cruise through the lymphatic system - principally the spleen and lymph nodes - seeking signs of foreign invaders. In this state, they are receptive to a type of chemical attractant, or chemokine called CXCL13, largely restricted to a neighborhood populated by other B cells and known simply as the "B zone".

But when stimulated by an antigen signal from a foreign microbe, the B cell doubles the number of receptors on its surface cued to a different group of chemical attractants known as CCL19 and CCL21, the researchers found. This makes all the difference, since these attractants are found in far greater concentration where T cells reside -- the "T zone." The increased receptiveness to these signals prompts the B cell to migrate within the lymphatic tissue from the B zone to the boundary between the B and T zones where cells of the two types can pair up. The pairing is known to be essential for th
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
6-Mar-2002


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