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

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:

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

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>