Featured Research

from universities, journals, and other organizations

Gene That Is Crucial For Antibody-producing Cell Development Is Key To Blood Cell Cancer

Date:
August 29, 2003
Source:
St. Jude Children's Research Hospital
Summary:
A gene that is crucial to the development and function of an entire family of immune cells is also key to understanding why one member of that family can become cancerous. Investigators at St. Jude Children's Research Hospital and the Blood Research Institute at the Blood Center of Southeastern Wisconsin, Milwaukee, reported this finding in the September 2003 issue of Nature Immunology.

MEMPHIS, TENN (August 27, 2003) -- A gene that is crucial to the development and function of an entire family of immune cells is also key to understanding why one member of that family can become cancerous. Investigators at St. Jude Children's Research Hospital and the Blood Research Institute at the Blood Center of Southeastern Wisconsin, Milwaukee, reported this finding in the September 2003 issue of Nature Immunology.

Related Articles


The St. Jude researchers had previously shown that one of these cell types, marginal-zone B cells, can give rise to a cancer called mucosa-associated lymphoid tissue (MALT) lymphoma when the cells abnormally over-express a gene called Bcl10. The current finding suggests that a drug that blocks the action of Bcl10 could be an effective treatment for this cancer.

The researchers discovered that Bcl10 activates a pathway of molecular signals that drives antibody-producing B cells to mature into one of three different members of this family of immune system cells: follicular, marginal zone and B1 B cells. Mice lacking Bcl10 have a significant decrease in mature B cells and cannot launch an effective antibody response against bacteria in their bloodstream.

To learn how Bcl10 controls B cell development and function, the investigators studied mice in which the gene was inactivated. The mice produced nearly normal numbers of immature B cells. However, these cells did not mature normally. This showed that Bcl10 function is essential for B-cell development.

The researchers found that mice lacking a functional Bcl10 gene could not activate specific pathways of signaling molecules that belong to a family of proteins called NF-κB. The NF-κB proteins are normally activated by Bcl10 after B cells encounter invading organisms, such as bacteria. These proteins then cause B cells to fully mature and release antibodies targeted against those specific organisms.

The central role of Bcl10 in B cell development and function is further evidence that this gene is a major contributor to the development of MALT lymphoma, according to St. Jude scientist Liquan Xue, Ph.D., the article's lead author.

"When Bcl10 jumps to a new location in a chromosome due to a genetic abnormality known as a rearrangement, it lands next to a section of DNA that forces the gene to be continually active," Xue said. "Bcl10 then continually activates the NF-κB proteins, driving the marginal-zone B cells to keep replicating themselves. That continual proliferation of the B cells leads to MALT lymphoma."

Demin Wang, an associate investigator at the Blood Research Institute, is the senior author of the article. He headed the work done at that location.

"Our discovery of the roles of Bcl10 in the development and functioning of B cells brings us a step closer to understanding how to control its activity and cure MALT lymphoma," Wang said. He is also an assistant professor at the Model Animal Research Center in Nanjing University, China, and at the Medical College of Wisconsin in Milwaukee.

The researchers also tested the ability of LPS, a molecule that forms part of the walls of some infectious bacteria, to stimulate marginal-zone B cells to multiply--a normal part of the body's infection response. Located mainly in the spleen, marginal-zone B cells usually multiply after binding with the LPS in bacteria, increasing the numbers of B cells releasing antibodies. In mice lacking the Bcl10 gene, however, LPS failed to stimulate B cells to proliferate normally. This observation showed that the gene is required for this type of B cell to respond to infections.

Mice lacking Bcl10 genes were infected with a strongly disease-causing strain of Streptococcus pneumoniae, which causes one of the most common forms of pneumonia in humans. Unable to clear up the infection, these mice died. However, mice with normal Bcl10 genes mounted immune responses to the infection and survived.

"This study is an example of how basic research can hold the promise of tangible benefits to people suffering from a particular disease," said Stephan Morris, M.D., an associate member of the St. Jude Pathology and Hematology-Oncology departments and one of the article's authors. Morris, one of the discoverers of Bcl10, initiated the current studies and directed the work at St. Jude.

###

Other authors of the study include Carlos Orihuela, Elaine Tuomanen, and Xiaoli Cui (St. Jude); and Renren Wen (Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee).

St. Jude Children's Research Hospital St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit http://www.stjude.org.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "Gene That Is Crucial For Antibody-producing Cell Development Is Key To Blood Cell Cancer." ScienceDaily. ScienceDaily, 29 August 2003. <www.sciencedaily.com/releases/2003/08/030829072844.htm>.
St. Jude Children's Research Hospital. (2003, August 29). Gene That Is Crucial For Antibody-producing Cell Development Is Key To Blood Cell Cancer. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2003/08/030829072844.htm
St. Jude Children's Research Hospital. "Gene That Is Crucial For Antibody-producing Cell Development Is Key To Blood Cell Cancer." ScienceDaily. www.sciencedaily.com/releases/2003/08/030829072844.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins