Freiburg researchers show how a protein prevents the uncontrolled expansion of immune cells
The mammalian immune system consists of millions of individual cells that are produced daily from precursor cells in the bone marrow. During their development, immune cells undergo a rapid expansion, which is interrupted by phases of differentiation to more mature lymphocytes.
Alternate phases of proliferation and differentiation occur also during the maturation of antibody-producing B cells. Researchers in Prof. Dr. Michael Reth’s laboratory have come one step closer to understand how the proliferation to differentiation switch in B lymphocytes works, thereby providing new insights into the development of the most common types of tumors in children and potential therapies thereof. The team has published its study in the journal Nature Immunology.
Because the switch induces differentiation, it limits the proliferation phase of precursor cells, so-called pre-B cells. If differentiation is blocked, pre-B cells continue to proliferate and this can lead to pre-B cell leukemia. The researchers have shown that the switch factor is a complex with two components: a small adaptor protein called B cell translocation gene 2 (BTG2) and the protein arginine methyl transferase 1 (PRMT1).
“We found that BTG2 is up-regulated upon pre-B cell differentiation and that an induced expression of BTG2 in pre-B cells stops their proliferation,” explains Dr. Elmar Dolezal, the first author of the published paper. How the BTG2/PRMT1 complex stops pre-B cell proliferation was shown by Dr. David Medgyesi: once activated by BTG2, PRMT1 specifically methylates the protein CDK4, thereby preventing its function in the cell cycle and further cell proliferation.
Interestingly, many tumor cells have either deleted the BTG2 gene or have silenced it. For example it is hardly expressed in B-Cell Acute Lymphoblastic Leukemia (B-ALL), the most common type of cancer in children. Using a mouse model, the authors of the study have shown that reintroducing BTG2 in such B-ALL tumor cells prevents further tumor development.
“We have discovered how BTG2 works as a tumor suppressor in pre-B cells and this may help to better understand and possibly develop a better treatment of B-ALL tumors,” summarizes Reth. “It will be important in the future to explore the exact mechanisms for expression and regulation of the BTG2 gene and to find ways in which we can introduce BTG2 in B-cell tumors to patients and thereby block the tumor cells’ proliferation.”
Michael Reth is Professor for Molecular Immunology at the Max Planck Institute for Immunology and Epigenetic (MPI-IE) and at the Faculty for Biology of the University of Freiburg. He is also director of the excellence cluster BIOSS, Centre for Biological Signaling Studies. This research was funded by the Max Planck Gesellschaft (MPG), the German Cancer Foundation and by the Deutsche Forschungsgemeinschaft via the collaborative research project 746, “Functional specificity through the coupling and modification of proteins”. Elmar Dolezal was funded by the Spemann Graduate School of Biology and Medicine at the University of Freiburg. David Medgyesi is one of the project leaders in Michael Reth’s laboratory.
Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J. Fiala, Susana Minguet, Bettina Warscheid, David M. Tarlinton, Hassan Jumaa, David Medgyesi & Michael Reth (2017): The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex. In: Nature Immunology. doi:10.1038/ni.3774
Prof. Dr. Michael Reth
E-Mail: BIOSS Centre for Biological Signalling Studies
University of Freiburg
Rudolf-Werner Dreier | idw - Informationsdienst Wissenschaft
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses