Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Important Regulator of Immune System Decoded

19.01.2016

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.


Cross section through a plasma cell (schematic diagram)

IMP

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."


Original Publications

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
IMP Communications
Research Institute of Molecular Pathology
Dr. Bohr-Gasse 7
A 1030 Vienna
hurtl@imp.ac.at
+43 (0)1 79730 3625

Media Contact at WEHI

Liz Williams
Media and Publications Manager
williams@wehi.edu.au 
+61 3 9345 2928 or 
+61 428 034 089

Weitere Informationen:

http://www.imp.ac.at/news/press-releases/
http://www.nature.com/ni/journal/vaop/ncurrent/pdf/ni.3349.pdf

Dr. Heidemarie Hurtl | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Gecko adhesion technology moves closer to industrial uses

13.12.2017 | Information Technology

Columbia engineers create artificial graphene in a nanofabricated semiconductor structure

13.12.2017 | Physics and Astronomy

Research reveals how diabetes in pregnancy affects baby's heart

13.12.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>