Prize Winner of the Paul Ehrlich and Ludwig Darmstaedter Prize 2014

PEPreistraeger_Reth_Fotograf_UweDettmar

Structural elucidation of B-cell antigen receptors

Before antibodies are produced, the immune cells responsible for this task must first be activated. Michael Reth has decoded important steps in this process.

The €100,000 Paul Ehrlich and Ludwig Darmstaedter Prize went 2014 to Michael Reth, Professor of Molecular Immunology at the Institute of Biology III of the Albert Ludwigs University Freiburg, Head of the Research Group at the Max Planck Institute of Immunobiology and Epigenetics and Director of the BIOSS Centre for Biological Signalling Studies in Freiburg, an excellence cluster. Reth has been awarded the prize for his outstanding achievements in the field of antibody research. "Michael Reth has demonstrated how the immune system's B cells are activated and induced to produce antibodies," wrote the Scientific Council of the Paul Ehrlich Foundation in explaining its decision. Reth has thereby helped to decode the molecular bases of Paul Ehrlich's famous side-chain theory.

The B cells entrusted with the production of antibodies are activated via the so-called antigen receptor. The receptor consists of a membrane-bound antibody and two further proteins, which Reth has discovered. These proteins act like heralds: they tell the B cell when a cognate antigen has docked on the antibody portion of the antigen receptor and help transmitting the signal for B cell activation. Reth has elucidated numerous molecular details of this signaling pathway. Errors in the signaling mechanism can lead to leukemia.

Reth's work has also disproven the cross-linking model of B cell activation that still persists in many textbooks. Every B cell carries about 120,000 antigen receptors. As the Paul Ehrlich and Ludwig Darmstaedter prize laureate was able to demonstrate, they do not occur singly on the surface but rather in groups. "The binding of an antigen destabilizes the group," Reth explains. "It then disintegrates into individual antigen receptors. This process of dissociation is what kicks off the activation of the B cells." The cross-linking model holds the opposite to be true: according to this model, the antigen receptor is activated by individual receptors associating together to form a group.

Since you can only really understand something if you put it together from its individual components, Reth uses the tools of synthetic biology in order to express the antigen receptor of mammals in the fruit fly. His next goal is to learn more about the protein landscape on the B cell's surface. "We've discovered that the membrane proteins in the range of 10 to 200 nanometers are arranged in a more orderly fashion than we had previously assumed," says Reth. "They are not distributed haphazardly on the B cell's surface but are organized in protein islands. It might also be possible to control the activation of the antigen receptor via the organization of these protein islands." Reth is anticipating a host of new knowledge about immune cells from this foray into the nanoworld.

Short biography of Professor Michael Reth

Michael Reth was born in 1950 in Düsseldorf. He studied biology in Cologne and obtained his doctorate from the Institute of Genetics of the University of Cologne. After a postdoctoral period at Columbia University in New York, he returned to Cologne in 1985 where he received his "Habilitation". In 1989 he moved to the Max Planck Institute of Immunobiology in Freiburg. In 1995 he was appointed Professor of Molecular Immunology at the Albert- Ludwigs University in Freiburg and continues to do research at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg. In 2007 Reth was appointed Director of the BIOSS Centre for Biological Signalling Studies, an excellence cluster. Michael Reth has received numerous awards: the Heinz Maier-Leibnitz Prize for Immunogenetics, the Gottfried Wilhelm-Leibniz Prize of the DFG, the EFIS-Schering-Plough-European Immunology Prize and an Advanced Grant of the European Research Council. Reth is a member of the German Academy of Sciences Leopoldina and of the European Molecular Biology Organization EMBO. He is also an Honorary Member of the American Association of Immunologists and sits on the editorial board of various specialist journals.

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