Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

One Path – Two Effects: Immune System uses DNA Repair Mechanism to Boost Defence

14.11.2006
Every day our immune system has to repel numerous pathogens. For this purpose defence cells produce specific antibodies which are tailored exactly to a particular pathogen. Since there are millions of different pathogens, many of which are extremely variable as well, this is an enormous challenge.

How does the immune system manage to keep pace with this diversity? For the first time scientists from the GSF – Research Centre for Environment and Health and the Max-Planck-Institute for Biochemistry in Martinsried could show that a molecular mechanism which is normally needed to repair damaged DNA pieces makes cells of the immune system particularly variable, so that they can react flexibly to a wide range of pathogens.

Certain defence cells of the immune system, the B-cells, are responsible for the production of specific antibodies. “These cells are the only body cells which can change their DNA by hypermutation, so that they form antibodies which are specifically tailored to the respective pathogen,” Prof. Jean-Marie Buerstedde, the Director of the GSF Institute of Molecular Radiation Biology, explains. Hypermutation is understood to be a considerably elevated mutation rate. The genes coding for specific antibodies mutate one million times more frequently than the genes of other cells.

It has been known for a long time that hypermutation is triggered by the enzyme AID. “AID is the master gene for hypermutation,” Buerstedde explains. It is B-cell-specific and causes a particular base of the DNA to be converted into another. This “wrong” base is then cut out of the DNA, which eventually creates a base gap. Buerstedde and his colleagues have now been able to prove that the following steps of the hypermutation make use of a mechanism which is also responsible for repairing damaged DNA. If the B-cell DNA is incomplete, the protein PCNA will be linked with another protein, ubiquitin – this mechanism activates certain emergency enzymes which mend the base gap as repair enzymes. PCNA ubiquitination also comes into action in normal body cells when the DNA is damaged: in this case, however, this mechanism ensures that DNA damage is repaired in a quick-fix procedure during the replication of the DNA. “Thus, PCNA ubiquitination is necessary both for DNA repair and for hypermutation,” Buerstedde explains.

PCNA ubiquitination in B-cells results in high mutation rates, since the emergency enzymes activated by this mechanism are highly likely to build not the original, but a different base into the DNA – the consequence being a point mutation. Several of these point mutations raise the affinity of the antibodies to a particular antigen and thus make the antibodies produced more effective. By antigen binding those B-cells are selected, which best bind the antigen and can, therefore, combat it most intensively. The remaining cells will die.

Thus, the immune system has tailored the path of PCNA ubiquitination for the use in B-cells for itself in such a way that high mutation rates occur in certain parts of the antibody genes. “On the one hand this is positive, because variable antibodies result. On the other hand, there is also the risk that uncontrolled mutations on wrong genes will contribute to the development of B-cell cancer. Therefore, the exploration of this path is of medical relevance,” Buerstedde emphasizes, “but for a geneticist it is just as exciting to realize that vertebrates adopted a path for the antigen-specific immune response, which has existed since primeval times”.

Michael van den Heuvel | alfa
Further information:
http://www.gsf.de/neu/Aktuelles/Presse/2006/buerstedde_en.php

Further reports about: Antibodies B-cell Buerstedde DNA Hypermutation Mutation PCNA enzyme ubiquitination

More articles from Life Sciences:

nachricht Scientists discover species of dolphin that existed along South Carolina coast
24.08.2017 | New York Institute of Technology

nachricht The science of fluoride flipping
24.08.2017 | University of North Carolina Health Care

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Scientists discover species of dolphin that existed along South Carolina coast

24.08.2017 | Life Sciences

The science of fluoride flipping

24.08.2017 | Life Sciences

Optimizing therapy planning for cancers of the liver

24.08.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>