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!
Communication between neural networks
17.12.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
Neurons migrate in the nascent brain as if on rails
17.12.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
17.12.2018 | Physics and Astronomy
17.12.2018 | Architecture and Construction
17.12.2018 | Life Sciences