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Key To Antibody Regulation Could Unlock New Treatments Via Immune System

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Cancer evades or wards off attack by the immune system and even hijacks some aspects of the body's defenses against disease to thrive and grow.  As some cancer researchers experiment with vaccines and other ways to turn the immune system against tumors, other scientists pursue a greater understanding of the basic components of immunity to build a foundation for future progress.

Researchers led by Chen Dong, Ph.D, Ph.D., of MD Anderson's Department of Immunology and Center for Inflammation and Cancer, have discovered an off switch for the mass production of antibodies launched by the immune system in response to a specific infection or type of abnormal cell. 

The specialized regulatory T cell that they identified blocks the swift production of antibodies in structures called germinal centers.  "We have known that regulatory T cells defend against unwanted or exaggerated immune system responses, but the mechanism by which they accomplish this was not known," Dong said.


Read the News Release
: Specialized Regulatory T Cell Stifles Antibody Production Centers


"In some types of cancer, the presence of many regulatory T cells is associated with poor prognosis," Dong said. "The theory is those cells suppress an immune system response in the tumor's microenvironment that otherwise might have attacked the cancer."

Their findings were published online this week at the journal Nature Medicine, two years after Dong and colleagues identified the molecular details behind a helper T cell that activates germinal centers - an on switch - in a publication in the journal Science

The twin discoveries raise the long-term possibility of regulating antibody production, with potential implications for treating cancer and autoimmune diseases.  Antibody production could be dialed down to deal with autoimmunity, or dialed up to attack cancers, although much research will be required to get to that point.

Germinal centers are found in the lymph nodes and the spleen. They serve as gathering points for B and T cell lymphocytes, infection-fighting white blood cells.

When the adaptive immune system detects an invader, B cells present a distinctive piece of it, called an antigen, to T cells.  The antigen converts a naïve T cell to a helper T cell that secretes cytokines, which help the B cells expand and differentiate into specialized antibodies to lead the attack on the intruder.

The Nature Medicine paper:  http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.2426.html

The Science paper: http://www.sciencemag.org/content/325/5943/1001.abstract?sid=6966a69c-74bb-465d-9068-9b5afaba8599

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