The discovery that a gene called Mcl-1 is critical for keeping this vital immune cell population alive was made by researchers at Melbourne's Walter and Eliza Hall Institute. Associate Professor David Tarlinton, Dr Victor Peperzak and Dr Ingela Vikstrom from the institute's Immunology division led the research, which was published today in Nature Immunology.
Antibody-producing cells, also known as plasma cells, live in the bone marrow and make antibodies that provide a person with long-term protection from viruses and bacteria, Associate Professor Tarlinton said. "Plasma cells are produced after vaccination or infection and are responsible for the immune 'memory' that can persist in humans for 70 or 80 years. In this study, we found that plasma cells critically rely on Mcl-1 for their continued survival and, without it, they die within two days," he said.
Dr Peperzak said the team was surprised to find that plasma cells used this as a 'failsafe' mechanism in controlling their survival. "One of the interesting things we found is that because plasma cells rapidly destroy Mcl-1 proteins within the cell yet depend on it for their survival, they need continuous external signals to tell them to produce more Mcl-1 protein," Dr Peperzak said. "This keeps the plasma cells under tight control, with Mcl-1 acting like a timer that constantly counts down and, if not reset, instructs the cell to die."
Plasma cells are vital to the immune response, but can be dangerous if not properly controlled, Associate Professor Tarlinton said. "As with any immune cell, plasma cells are really quite dangerous in many respects and need to be tightly controlled," he said. "When they are out of control they continue to make antibodies that can be very damaging if there are too many. This happens in conditions such as myeloma – a cancer of plasma cells – and various forms of autoimmunity, such as systemic lupus erythamatosus or rheumatoid arthritis, where there are excessive levels of antibodies."
Myeloma is a blood cancer that affects more than 1200 Australians each year, and is more common in people over 60. It is caused by the uncontrolled production of abnormal plasma cells in the bone marrow and the build up of damaging antibodies in the blood. Rheumatoid arthritis and lupus are autoimmune diseases in which the antibodies produced by plasma cells attack and destroy the body's own tissues.
Associate Professor Tarlinton said that his hope was that the discovery could be used to develop new treatments for these conditions. "Myeloma in particular has a very poor prognosis, and is generally considered incurable," Associate Professor Tarlinton said. "Now that we know Mcl-1 is the one essential gene needed to keep plasma cells alive, we have begun 'working backwards' to identify all the critical molecules and signals needed to switch on Mcl-1 and keep the cells alive. Our hope is that we will identify some point in the internal cell signalling pathway, or a critical external molecule, that could be blocked to stop Mcl-1 being produced by the cell. This would be an important new platform for diseases that currently have no specific or effective treatment, such as myeloma, or offer new treatment options for people who don't respond well to existing treatments for diseases such as lupus or rheumatoid arthritis."
This research was supported by the National Health and Medical Research Council of Australia, Multiple Myeloma Research Foundation, European Molecular Biology Organization and the Victorian Government.
Liz Williams | EurekAlert!
A room with a view - or how cultural differences matter in room size perception
25.04.2017 | Max-Planck-Institut für biologische Kybernetik
Studying a catalyst for blood cancers
25.04.2017 | University of Miami Miller School of Medicine
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Earth Sciences
25.04.2017 | Life Sciences
25.04.2017 | Earth Sciences