Specialized regulatory T cell stifles antibody production centers

July 25, 2011

A regulatory T cell that expresses three specific genes shuts down the mass production of antibodies launched by the immune system to attack invaders, a team led by scientists at The University of Texas MD Anderson Cancer Center reported online in the journal Nature Medicine.

"Regulatory T cells prevent unwanted or exaggerated responses, but the mechanism by which they accomplish this has been unclear," said paper senior author Chen Dong, Ph.D., professor in MD Anderson's Department of Immunology and director of the Center for Inflammation and Cancer.

"We've identified a molecular pathway that creates a specialized regulatory T cell, which suppresses the reaction of structures called germinal centers. This is where immune system T cells and interact to swiftly produce large quantities of antibodies," Dong said.

The discovery of the germinal center off-switch, which comes two years after Dong and colleagues identified the mechanisms underlying a helper T cell that activates the centers, has potential implications for cancer and .

"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 in the tumor's microenvironment that otherwise might have attacked the cancer."

However, in B cell lymphomas, overproliferation and mutation of B cells are the problems, Dong said. Hitting the regulatory T cell off-switch might help against lymphomas and autoimmune diseases, while blocking it could permit an immune response against other cancers.

Antibody production central

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

When the detects an invading bacterium or virus, B cells present a piece of the invader, 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 destroy the intruder.

"Germinal centers have mostly B cells with a few helper T cells to regulate them. The B cells mutate to make high-affinity antibodies and memory B cells for long-term immunity. The cell population in the germinal center structures replicates in an average of several hours, one of the fastest rates of cell replication known in mammals," Dong said.

Tracking down specialized T cell

In the Nature Medicine paper, Dong and colleagues found that a subgroup of regulatory T cells that expresses two genes, Bcl-6 and CXCR5, moves into germinal centers in both mice and humans, where they have access to B cells.

(Bcl-6 produces a protein called a transcription factor, which moves into the cell nucleus to regulate other genes. CXCR5 is a receptor protein for a signaling molecule called CXCL13.)

They also found that the Bcl-6/CXCR5 T cells aren't produced in the thymus, with other T cells, but are generated by regulatory T cell precursor cells that express Foxp3, another transcription factor.

Knocking out the that express all three proteins in mice resulted in increased germinal center production of antibodies. They named this key T cell the T follicular regulatory cell, or Tfr.

In a 2009 paper in the journal Science, the researchers found that naïve T cells that expressed Bcl-6 and CXCR5 also gathered in the B cell zone of germinal centers. Expression of Bcl6 converted the T cell into a T follicular helper (Tfh) cell that launches in the germinal centers.

With Tfr turning germinal centers off and Tfh turning them on, we could potentially regulate antibody production, Dong noted. Increasing Tfr production could be a new approach to treating autoimmune inflammatory disorders, such as lupus and rheumatoid arthritis.

Explore further: Awaiting orders to retaliate

Related Stories

Awaiting orders to retaliate

June 24, 2011
(Medical Xpress) -- When immune system B cells are alerted to the presence of a threat within the body, they form structures called germinal centers, which serve as ad hoc headquarters for marshaling a targeted immune response. ...

Recommended for you

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

New technique overcomes genetic cause of infertility

August 17, 2017
Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

Inhibiting a protein found to reduce progression of Alzheimer's and ALS in mice

August 17, 2017
(Medical Xpress)—A team of researchers with Genetech Inc. and universities in Hamburg and San Francisco has found that inhibiting the creation of a protein leads to a reduction in the progression of Alzheimer's disease ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.