Plasma cells play a key role in our immune system. Now scientists at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria, and at the Walter and Eliza Hall Institute (WEHI) in Melbourne, Australia, succeeded in characterizing a central regulator of plasma cell function. The results of both teams are published in two back-to-back papers in “Nature Immunology” today.
Our environment teems with microorganisms and viruses that are potentially harmful. The reason why we survive their daily attacks is the ability of the immune system to neutralize these invaders in numerous ways. Plasma cells are key players in this process. They fight infections and establish long-lasting protection against pathogens.
Plasma cells are white blood cells that develop from B-cells. They are the effector cells of the humoral immune response. Their main function is to produce antibodies that patrol the body in large numbers to neutralize harmful invaders. A functional plasma cell produces up to 10,000 antibodies per second to release them into the blood stream.
This outstanding achievement can be visualized with a powerful microscope, as active plasma cells are packed with antibody-producing vesicles, constituting the so-called endoplasmic reticulum that is essential for antibody assembly and secretion.
B-cells need to be activated by antigens (foreign substances) in order to develop into plasma cells. They first form plasmablasts that migrate to the bone marrow where they survive for many years or even decades. The long-lasting protection provided by active vaccines is based on this immunological memory of plasma cells.
A Central Role for Blimp1
Scientist have known about the functions of plasma cells for quite a while. However, details of how the differentiation and function of these cells are regulated were still unknown. Now an important key to understanding the function of plasma cells has been discovered by a team headed by Meinrad Busslinger, Senior Scientist and Deputy Director at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria.
In a five-year project, the team succeeded in deciphering the role of the protein Blimp1 as a central regulator of plasma cell development and function. In its current issue, the science journal Nature Immunology publishes the results of the team in Vienna as well as the work of Australian colleagues that complements the Viennese results.
In detailed studies, scientists at the IMP identified all genes that are involved in the development of plasma cells in mice. First author Martina Minnich, whose PhD-thesis provided the groundwork for the publication, explains the results: "We found that more than 50 percent of these genes are regulated by Blimp1.
Therefore, this factor must be of vital importance for plasma cells. Furthermore, we were able to show for the first time that Blimp1 not only switches genes off but can also switch other genes on. This is an important discovery for the understanding of plasma cell development."
"Most of the essential functions of plasma cells are controlled by the factor Blimp1", Meinrad Busslinger summarizes the results. "It regulates their mobility and migration to the bone marrow. Blimp1 is also responsible for the enormous increase in size of the endoplasmic reticulum and the strong up-regulation of antibody production in plasma cells. Humoral immunity would not be possible without Blimp1."
No Antibodies without Blimp1
Even though Blimp1 is necessary for the development of plasma cells, mature plasma cells can survive without this factor. However, when Blimp1 is switched off, they become non-functional as they no longer produce antibodies. This unexpected finding is the result of work carried out at the Walter and Eliza Hall Institute (WEHI) in Melbourne, Australia. The study, which is published back-to-back with the Austrian paper, was led by Stephen Nutt, Head of the Division of Molecular Immunology at WEHI. The picture that emerges from the Australian study perfectly complements the results obtained at the IMP.
Insight into the manifold functions of Blimp1 is not only important for our understanding of the immune system but may also be relevant for human medicine. Mutations in the Blimp1 gene can block the further differentiation of B-cells, which contributes to the formation of malign B cell tumors known as lymphomas. Moreover, quiescent plasma cells can sometimes switch to uncontrolled cell growth and thus turn into plasma cell tumors or multiple myelomas.
Another aspect of the immune system that is highly relevant for medicine is the broad spectrum of autoimmune diseases. Conditions like systemic lupus erythematosus (SLE) are an example for the serious damage to organs and tissue caused by misguided immune responses which generate plasma cells producing auto-reactive antibodies that turn against the body’s own tissue.
Meinrad Busslinger: "The published results have yielded profound insight into the function of plasma cells. They also raise new interesting questions which we will address in forthcoming projects."
Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation. Martina Minnich et al. Published online in Nature Immunology on 18 January 2016; doi:10.1038/ni.3349
Blimp1 controls plasma cell function through regulation of immunoglobulin secretion and the unfolded protein response. Julie Tellier et al. Published online in Nature Immunology on 18 January 2016; doi: 10.1038/ni.3348
About the IMP
The Research Institute of Molecular Pathology (IMP) in Vienna is a basic biomedical research institute largely sponsored by Boehringer Ingelheim. With over 200 scientists from 37 nations, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. Research areas include cell and molecular biology, neurobiology, disease mechanisms and computational biology.
Media Contact at the IMP
Dr. Heidemarie Hurtl
Research Institute of Molecular Pathology
Dr. Bohr-Gasse 7
A 1030 Vienna
+43 (0)1 79730 3625
Media Contact at WEHI
Media and Publications Manager
+61 3 9345 2928 or
+61 428 034 089
Dr. Heidemarie Hurtl | idw - Informationsdienst Wissenschaft
Funding of Collaborative Research Center developing nanomaterials for cancer immunotherapy extended
28.06.2017 | Johannes Gutenberg-Universität Mainz
Zeolite catalysts pave the road to decentral chemical processes Confined space increases reactivity
28.06.2017 | Technische Universität München
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
28.06.2017 | Physics and Astronomy
28.06.2017 | Physics and Astronomy
28.06.2017 | Health and Medicine