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."