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The structure behind the switch

April 6, 2003--A team of scientists from the Keck School of Medicine of USC has, for the first time, described a new, stable DNA structure in both mouse and human cells-one which differs from the standard Watson-and-Crick double helix and plays a critical role in the production of antibodies, or immunoglobulins.

The research will be published online in the journal Nature Immunology this week, and will appear in print in the journal's May issue.

"The way in which the five different immunoglobulin classes are created is a nearly perfect system," notes Michael Lieber, M.D., Ph.D., professor of pathology and biochemistry and the study's principal investigator. "And yet, the DNA mechanism for how a cell switches from producing one class to producing another has remained a mystery for almost 20 years."

The typical antibody molecule is shaped like the letter Y. The region at the end of each of the two short arms houses the receptors that recognize and bind with a specific foreign object, or antigen. These receptors are created via a well-described cutting-and-splicing mechanism that occurs within the nuclear DNA of B cells, which are key components of the immune system.

The long stem, or handle, of the Y determines to which immunoglobulin class an antibody belongs. It, too, is created via a B-cell nuclear cut-and-paste job, but the mechanics here are much more complicated-and until now, much less well understood.

An immunoglobulin's class is important because it determines where in the body the antibody's efforts will be concentrated. While immunoglobulin M (IgM) works mostly in the bloodstream, for instance, IgG can easily slip through a capillary's walls and cross the placenta, and IgA can make itself at home in the lungs, the digestive tract and the body's secretions (saliva, sweat, tears).

Although antibodies are needed in all areas of the body, they all begin life as IgM, explains Kefei Yu, Ph.D., the paper's first autho
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Contact: Lori Oliwenstein
oliwenst@usc.edu
323-442-2830
University of Southern California
6-Apr-2003


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