Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Specialized regulatory T cell stifles antibody production centers

Discovery has potential implications for cancer, autoimmune disease

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 immune system 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 B cells 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 autoimmune diseases.

"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."

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 white blood cells.

When the adaptive immune system 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 regulatory T cells 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 antibody production 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.

The team's research was funded by grants from the National Institutes of Health, the Leukemia and Lymphoma Society, MD Anderson, the American Heart Association, Doris Duke Charitable Foundation Clinical Scientist Development Award and the China Ministry of Science and Technology Protein Science Key Research Project.

Co-authors with Dong are first author Yeonseok Chung, Ph.D., Shinya Tanaka, Ph.D., Roza Nurieva, Ph.D., Gustavo Martinez, Yi-Hong Wang and Joseph Reynolds, Ph.D., of MD Anderson's Department of Immunology and the Center for Cancer Immunology; Chung also is with The University of Texas Health Science Center at Houston Institute of Molecular Medicine; Seema Rawal and Sattva Neelapu, M.D., of MD Anderson's Department of Lymphoma and Myeloma, also of the Center for Cancer Immunology; and Ziao-hui Zhou, M.D., Hui-min Fan, M.D., and Zhong-ming Liu, M.D., of Shanghai Dong Fang Hospital, Shanghai, China.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For eight of the past 10 years, including 2011, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>