Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Evolution in the antibody factory

11.03.2013
How immune cells are able to advance their own evolution

Immune system B cells play a crucial role in the defence of pathogens; when they detect such an intruder, they produce antibodies that help to combat the enemy. They concurrently and continuously improve these molecules to more precisely recognize the pathogens.


Theory of colours for immunologists – sophisticatedly-designed microscopy technologies offer scientists insights into the evolution of antibody producers in the lymph node. Antibodies and immune cells are marked with different colours.
University of Birmingham/Toellner

A team of scientists with participation of the Helmholtz Centre for Infection Research (HZI) has discovered that during this process the cells are able to advance their own evolution themselves by increasing the selection pressure through previously-produced antibodies. The results are also significant for the development of new vaccination strategies.

The principle of evolution signifies the competition for limited resources and a reaction to changeable environmental conditions. This selection pressure is virtually produced by the B cells on their own; they subject themselves to an optimization cycle in the lymph node, a process which only a few of them survive, i.e. particular cells that are able to produce “better” antibody molecules as compared to those that already exist within the body. The quality of these antibodies is tested in the lymph nodes, and only those cells that are able to prove themselves here receive signals from other immune cells that assure their survival.

Every B cell carries a specific defence molecule on its surface. It recognizes certain structures of pathogens – so-called antigens – similar to the way a key fits into one specific lock. This molecule is furthermore produced in a certain form that does not remain on the cell surface; rather, it travels with blood and lymph throughout the body. If the antibody encounters an antigen, it either binds it to neutralise it, or it sends out an alarm to other players within the immune system.

At the beginning of an infection there are, figuratively speaking, several keys that do not yet fit properly. This changes in the course of a process that immunologists refer to as “somatic hypermutation”: B cells mutate those gene segments that determine the design of both the surface molecule and the soluble variation – thus influencing how strongly the antibodies attach themselves to the pathogens. Those cells, in which the optimal fit of the key increases, survive and multiply. They then produce the desired molecule in large quantities and thus help us to get healthy again.

But how do the immune cells know that they are on the right way with this arbitrary mutation process, i.e. that the key will fit better later on? Scientists from England, Germany and Switzerland have now been able to answer this question jointly in a collaborative project between Dr. Kai-Michael Toellner, University of Birmingham, and Prof. Michael Meyer-Hermann, Head of the Department Systems Immunology. They published their findings in the renowned Journal of Experimental Medicine. Meyer-Hermann makes use of mathematical models to understand diseases more thoroughly and quicker. “Systems immunology enables us to simulate, in a short amount of time, numerous experimental conditions,” he describes his area of expertise. With the aid of such mathematical simulations followed by experimental examinations, the researchers discovered that the antibody producers advance their own evolution, which represents without a doubt an alignment with the enormous selection pressure that we are subject to due to a constant threat from pathogens.

The stage for this process is the so-called germinal centres within the lymph nodes. Here, the maturing B cells encounter the antigens. The researchers’ results suggest that completed antibodies from all germinal centres re-appear at the sites of antibody production and bind there to pathogen fragments as well. They represent competition thereby for those cells that are still in the process of refining the optimal fit of their surface molecules. Once the immune cells with their “surface-key” are able to bind to the “antigen locks” more readily than the finished antibodies, they receive survival signals and their key-form asserts itself.

“This is the ‘survival of the fittest’ as previously described by Charles Darwin on a molecular level,” compares Meyer-Hermann. Studies with mice were able to be confirmed in computer simulations only under the assumption that the B cells compete with their own products – namely the antibodies – for the right to bind to antigens.

This astounding mechanism could, in the future, improve conventional vaccination methods. “It is plausible that patients could be administered, in addition to a vaccine, sufficiently-strong-binding antibodies,” explains Meyer-Hermann. “Our models constructed in the computer suggest that this method accelerates the process of identifying optimal antibodies.” The scientists suspect that the addition of antibodies manipulates the reaction to vaccination, since the newly-generated antibodies are now in competition with the externally-introduced molecules. The conditions for selection are thus intensified and the B cells react by producing optimal antibodies earlier on. The result is that vaccinations could take effect quicker.

Original publication:
Yang Zhang*, Michael Meyer-Hermann*, Laura A. George, Marc Thilo Figge, Mahmood Khan, Margaret Goodall, Stephen P. Young, Adam Reynolds, Francesco Falciani, Ari Waisman, Clare A. Notley, Michael R. Ehrenstein, Marie Kosco-Vilbois and Kai-Michael Toellner, *shared first authorship.
Germinal center B cells govern their own fate via antibody feedback
Journal of Experimental Medicine, 2013, doi: 10.1084/jem.20120150
The Department “Systems Immunology“ at the HZI studies mathematical modelling of immunological issues. The department is associated with the Braunschweig Integrated Centre for Systems Biology (BRICS), a new research centre for systems biology jointly founded by the HZI and the Technische Universität Braunschweig.

Dr. Birgit Manno | Helmholtz-Zentrum
Further information:
http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/evolution_in_the_antibody_factory/

More articles from Life Sciences:

nachricht Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory

nachricht ‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

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

Midwife and signpost for photons

11.12.2017 | Physics and Astronomy

How do megacities impact coastal seas? Searching for evidence in Chinese marginal seas

11.12.2017 | Earth Sciences

PhoxTroT: Optical Interconnect Technologies Revolutionized Data Centers and HPC Systems

11.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>