Flexibility may be a crucial advantage in the defence against pathogens
When a foreign substance invades a body, the body produces antibodies that recognise and fight the intruder by means of antibodies that bind to a specific portion of the intruder - the antigen. Memory cells are then formed in the course of the defence reaction.
These cells make sure that the body can respond more quickly and more strongly to any recurring attack of the same pathogen. According to a study just published in "Science" by scientists of the Whitehead Institute for Biomedical Research, Cambridge, USA, and the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, the common notion, i.e. that the body produces antibodies with a perfectly fitting key-lock design for a specific antigen exclusively, is not true.
Antibodies are produced by a certain type of white blood cells called B-cells or B-leukocytes which patrol our lymph nodes in search of pathogens every day. When a B-cell binds to an antigen by means of its receptor, the B-cell either produces a reasonably well-fitting antibody directly or it gets involved in the formation of a germinal centre. Germinal centres are antibody training sites:
The B-cells proliferate in them, diversify their antibodies through mutation and optimise them through selection. "In the course of time, the affinity of the antibodies for the antigens increases. Basically, only the most effective antibodies persist. This evolutionary process is called affinity maturation," says Michael Meyer-Hermann, who is the director of the "System Immunology" department at the HZI.
Meyer-Hermann and his colleague, Gabriel Victora, from the Whitehead Institute for Biomedical Research aimed to test this theory in the scope of a project funded by the Human Frontiers Science Program in order to find out more about the process of affinity maturation. For this purpose, the researchers combined single-cell sequencing with brainbow experiments, a technique that is common in brain and developmental research. In this technique, mother cells are stained with random fluorescent proteins, which they then pass on to their daughter cells.
"This allows us to recognise exactly which lineage the cells have come from, and which founder cells dominate the germinal centre," says Meyer-Hermann. "According to what was known, we presumed that only a few cells established the germinal centre and that the strong selection pressure would lead to uni-coloured germinal centres."
The results of the sequencing were astounding: "According to common belief, there are on the order of three to five founder cells per germinal centre. We just showed that the number is closer to 100," says Meyer-Hermann. The brainbow experiments showed that the germinal centres do not become as uni-coloured as expected. While some centres turned uni-coloured in the course of the antibody selection process, there were others which consisted of different colours even after a long period of time.
This means that there is not one definite dominant antibody, but that many different antibodies coexist.
Perhaps it is not always of advantage to adapt perfectly to a pathogen. After all, the pathogens keep developing too. "The more specific the antibodies are, the more difficult it may be for them to respond to mutations in the pathogens," says Meyer-Hermann. "Accordingly, a certain degree of variability and flexibility could be crucial for keeping up with the constantly changing pathogens."
In the long term, these insights might help in the development of new vaccines, since antibodies are the fundamental basis of vaccines. "Once we know what affects the ratio of dominant-clone versus diverse germinal centres, we can specifically adapt the diversity of the induced antibodies to the mutation rate of the pathogen in the vaccination protocols we use," says Meyer-Hermann.
Susanne Thiele | Helmholtz-Zentrum für Infektionsforschung
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Life Sciences
23.03.2018 | Materials Sciences
23.03.2018 | Process Engineering