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Backstage with a command performer

Some cells sing with the chorus, while others unwittingly achieve fame on their own. The immune system's B cell is a true diva that spends its early days preparing for the ultimate audition. Its repertoire of possible antibodies to invading microbes totals 50 million. For the immune system, this repertoire means the difference between destroying a potentially lethal antigen or not.

Since the late 1970s, the genes for making immunoglobulin, a family of blood proteins that compose the antibodies, sufficed to explain the B cell's vast oeuvre. A B cell that is mature enough to respond to antigen does so by combining genes in a process called immunoglobulin gene rearrangement. Many possible combinations during this process allow a wide catalog of antibodies to literally take shape. Now, a biochemical phenomenon involving changes to stationary proteins in the B cell's nucleus, called histones, is known also to contribute to the cell's various solo performances.

In the February 2003 issue of Nature Immunology, Sasha Tarakhovsky and his Rockefeller University colleagues reveal that a little-studied regulating protein, Ezh2, carries out an important mission on histone H3 protein in developing B cells. In other words, a new criterion defining B cells' uniqueness has been discovered.

The finding, while vitally important to understanding the B cell and its immune system counterparts, represents a first in determining the physiological effects of changes wrought on the chromatin fiber -- the material basis of chromosomes made of DNA "thread" wound on protein "spools" called histones.

"We knew we could use our existing genetic tools to move from studying B cell signaling at the antigen receptor on the cell's surface to that occurring in the cell's nucleus," says Tarakhovsky. "Ezh2 in early B cell development means the difference between 50 million antibody possibilities versus 50,000 in mice without Ezh2."

A biochemical theory bears p
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Contact: Lynn Love
lovel@rockefeller.edu
212-327-8977
Rockefeller University
20-Feb-2003


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