Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MDC Researchers Solve Puzzle of B-Cell Lymphoma Development

24.09.2012
In the germinal centers of the lymphatic system B cells produce antibodies specific for the pathogen. However, most lymphomas derive from the B cells at the germinal centers.

Now, Dr. Dinis Pedro Calado and Dr. Klaus Rajewsky of the Max Delbrück Center (MDC) have identified subgroups of B cells in germinal centers in which the proto-oncogene Myc, a critical regulator of cellular proliferation, is highly activated.


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.

(Photo: Dinis Calado/ Copyright: MDC)

They showed that the Myc gene in these subpopulations is essential for the formation and maintenance of the germinal centers. Their findings also shed light on the origin of B-cell lymphomas derived from B cells at the germinal center (Nature Immunology, DOI:10.1038/ni.2418)*.

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 Myc gene 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.

*The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers

Dinis Pedro Calado1,2, Yoshiteru Sasaki3, Susana A. Godinho4, Alex Pellerin1, Karl Köchert2, Barry P. Sleckman5, Ignacio Moreno de Alborán6, Martin Janz2,7, Scott Rodig8, & Klaus Rajewsky1,2

1Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, USA. 2Max Delbrück Center for Molecular Medicine, Berlin, Germany. 3Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 4Department of Pediatric Oncology, Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA. 5Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. 6Department of Immunology and Oncology, National Centre for Biotechnology, Madrid, Spain. 7Hematology, Oncology and Tumor Immunology, Charité, University Medical School, Berlin, Germany. 8Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Contact:
Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de/

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>