Featured Research

from universities, journals, and other organizations

Researchers solve puzzle of B-cell lymphoma development

Date:
September 23, 2012
Source:
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Summary:
In germinal centers, immune cells learn to fight pathogens with high specificity. Researchers have now identified subpopulations of B cells at the germinal centers which express the proto-oncogene Myc (red). They showed that Myc is essential for the formation and maintenance of germinal centers. Their findings have implications for the pathogenesis of B-cell lymphomas.

In germinal centers (here: whithin the spleen of a mouse) immune cells learn to fight pathogens with high specificity. Dr. Dinis Calado and Dr. Klaus Rajewsky now identified subpopulations of B cells at the germinal centers which express the proto-oncogene Myc (red). They showed that Myc is essential for the formation and maintenance of germinal centers. Their findings have implications for the pathogenesis of B-cell lymphomas.
Credit: Dinis Calado/ Copyright: MDC

Germinal centers are sites in the organs of the lymphatic system, formed during the course of an immune response to infection, where B cells intensely proliferate and modify their DNA in order to produce antibodies specific for the pathogen. However, it is known that the vast majority of lymphomas derive from the B cells at the germinal centers. Now, Dr. Dinis Pedro Calado and Dr. Klaus Rajewsky of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have identified subgroups of B cells in germinal centers in which the proto-oncogene Myc, a critical regulator of cellular proliferation, is highly activated. They showed in addition that the Myc gene in these subpopulations is essential for the formation and maintenance of the germinal centers.

Their findings, published in Nature Immunology, also shed light on the origin of B-cell lymphomas derived from B cells at the germinal center reaction.

The Myc gene is a key regulator of cellular proliferation and is frequently involved in chromosomal translocations in human lymphomas derived from B cells at the germinal center reaction. Such translocations, seen in roughly 10 percent of diffuse large B-cell lymphomas and almost all cases of sporadic Burkitt lymphoma, juxtapose Myc and enhancers in immunoglobulin loci, leading to deregulated Myc expression.

These observations have puzzled researchers for many years because translocations of this gene can only take place in those cells where Myc is active. "However, Myc is thought not to be expressed in B cells at the germinal center reaction, the progenitors of most B-cell lymphomas," Dr. Rajewsky said. So the question was: if B cells at the germinal center reaction do not express Myc, how can they give rise to B cell lymphomas carrying Myc translocations?

Germinal centers are located in the lymphatic organs such as the spleen, lymph nodes and Peyer's patches in the intestinal wall. In the germinal centers the B cells are confronted with antigens and quickly proliferate. For the immune system to be able to cope with the huge variety of antigens, B cells must modify their DNA through mutation (somatic hypermutation) and recombination (class-switch recombination). However, the fast proliferation together with the ongoing DNA modifications may increase the occurrence of errors, which makes the malignant transformation of B cells at the germinal center reaction probable. "B-cell lymphomas are the most common type of human lymphoid malignancies. They mostly originate either from B cells at the germinal center reaction or from B cells that have passed through the germinal center reaction," Dr. Calado and Dr. Rajewsky pointed out.

What then is the role of the Myc gene? How can Myc be highly activated through translocations in B-cell lymphomas although it is not active in healthy B cells of the germinal center reaction? Dr. Calado and Dr. Rajewsky have now found an answer to this question. They identified subpopulations of B cells located in the germinal centers in which the Myc gene is activated. They also showed that c-Myc is essential for the formation and maintenance of the germinal centers. When they knocked out the Mycgene in B cells they could show that germinal centers could not be formed or maintained.

"The MYC-positive germinal center B-cell subpopulations are probably at high risk for malignant transformation. Our work has direct implications for the understanding of the pathogenesis of human germinal center-derived B-cell lymphomas carrying MYC chromosomal translocations and therefore can contribute to a better understanding of how these lymphomas occur," Dr. Calado and Dr. Rajewsky said.


Story Source:

The above story is based on materials provided by Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. Note: Materials may be edited for content and length.


Journal Reference:

  1. Dinis Pedro Calado, Yoshiteru Sasaki, Susana A Godinho, Alex Pellerin, Karl Köchert, Barry P Sleckman, Ignacio Moreno de Alborán, Martin Janz, Scott Rodig, Klaus Rajewsky. The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers. Nature Immunology, 2012; DOI: 10.1038/ni.2418

Cite This Page:

Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. "Researchers solve puzzle of B-cell lymphoma development." ScienceDaily. ScienceDaily, 23 September 2012. <www.sciencedaily.com/releases/2012/09/120923145104.htm>.
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. (2012, September 23). Researchers solve puzzle of B-cell lymphoma development. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2012/09/120923145104.htm
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. "Researchers solve puzzle of B-cell lymphoma development." ScienceDaily. www.sciencedaily.com/releases/2012/09/120923145104.htm (accessed August 28, 2014).

Share This




More Health & Medicine News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) — State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) — The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) — CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. Video provided by Newsy
Powered by NewsLook.com
How A 'Rule Of Thumb' Could Slow Down Drinking

How A 'Rule Of Thumb' Could Slow Down Drinking

Newsy (Aug. 28, 2014) — A study suggests people who follow a "rule of thumb" when pouring wine dispense less than those who don't have a particular amount in mind. 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:
from the past week

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