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Study offers clues to origins of autoimmunity

Researchers at National Jewish Medical and Research Center have discovered a mechanism in the body that could lead to autoimmune diseases, such as lupus, rheumatoid arthritis, or diabetes. The research team, led by John Cambier, Ph.D., found that potentially harmful B cells circulating in the body are not permanently silenced as previously thought; they can awaken and regain the ability to launch an attack against the body's own tissue. The findings were published online October 2 by Nature Immunology.

"Keeping self-reactive B cells in a quiescent state is crucial for the prevention of autoimmunity," said Dr. Cambier, Professor and Chairman of the Integrated Department of Immunology at National Jewish and the University of Colorado Health Sciences Center. "Our findings show how these cells can be reactivated and suggest lines of research that may lead to therapies for autoimmune diseases."

B cells are part of the immune system. When properly stimulated, they produce antibodies, which bind to foreign molecules and neutralize them or target the cells they are part of for destruction. The body, in its attempt to protect against any foreign invader, produces a huge variety of B cells, each capable of recognizing a different molecule, also called an antigen.

However, in the course of generating such a variety of B cells, the immune system also produces ones that recognize normal components of the body as antigens. Were those cells to become activated, they would initiate an attack against the body's own tissue. Fortunately, these cells are sent into a sort of suspended animation, known as anergy, when they encounter the antigen but fail to receive additional signals necessary to activate their antibody-producing machinery.

For years, scientists have thought that one encounter with an antigen would send a B cell into permanent anergy. Dr. Cambier and his colleagues showed, however, that self-reactive B cells need constant stimulation by
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Contact: William Allstetter
allstetterw@njc.org
303-398-1002
National Jewish Medical and Research Center
2-Oct-2005


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