03 / 2023
Each year, the Paul Ehrlich Foundation awards the Paul Ehrlich and Ludwig Darmstaedter Prize to one or more researchers who have made special contributions to the research fields for which Paul Ehrlich was an advocate. Contributions to the fields of immunology, cancer research, haematology, microbiology and chemotherapy are of particular significance. The award ceremony traditionally takes place on Paul Ehrlich's birthday, the 14th of March, in the St. Paul's Church (Paulskirche) in Frankfurt. This year, immunologists Frederick W. Alt (73), Harvard Medical School, and David G. Schatz (64), Yale Medical School, were awarded the €120,000 prize. They have discovered molecules and mechanisms that enable the immune system to recognise billions of different antigens at first contact and to form specific antigen antibodies. Following tradition, the two prize winners accepted the invitation issued by the Paul-Ehrlich-Institut and presented their research on 15 March 2023 as part of a scientific colloquium.
From left to right: Frederick W. Alt, Prof. Dr. Klaus Cichutek, David G. Schatz (Source: B.Morgenroth / Paul-Ehrlich-Institut)
B cells and T cells are white blood cells (lymphocytes). These cells, together with antibodies, make up the acquired (specific) immune system, which can adapt to and fight new pathogens. One way that the immune system recognises pathogens is with its billions of precursor B cells, each of which carries an antigen receptor on its surface. However, the antigen receptors differ amongst the B cells.
The B cell antigen receptors recognise structures of a pathogen. Viruses are often recognised by specific protein structures on the virus surface. The pathogen components, known as antigens, and the antigen regions, known as epitopes, are both identified by the immune system. B cells that recognise epitopes of a pathogen release antibodies that carry the recognition structures of their antigen receptor and therefore also recognise the epitopes on the pathogen surface. They can then bind to antigens and intercept pathogens in this way.
The genes with the information for the formation of the B cell antigen receptors consist of different building blocks (gene segments) and are combined with each other randomly in each B cell to form a unique antibody gene in the B cell. This process, called somatic recombination, produces B cells with varying, random antigen specificities. The prize winners, Alt and Schatz, have explored the details of somatic recombination.
David G. Schatz contributed to the elucidation of the mechanism of V(D)J recombination. He discovered that the enzyme complex RAG1/2 cuts random sections from three relatively far apart sections on the DNA specifically for each antibody. The name V(D)J recombination comes from the names for the individual gene segments (V for variable, D for diversity, J for joining). Frederick Alt discovered the repair enzymes, which link the excised sections together.
Schatz and Alt have also helped to elucidate somatic hypermutation, in which the normal mutation rate is increased millions of times in the regions of the V segments by an enzyme. The two scientists were able to show how this enzyme works very precisely. These findings are of great value for the question of how this mutational ability can be used for the maturation of antibodies without running the risk of tumour formation occurring as a result of the mutations.
"With their basic research, the prize winners Alt und Schatz have made a decisive contribution to a better understanding of the functioning of our immune system. As a result of their work, translational research in biomedicine can open up new therapeutic perspectives in which our immune system's capabilities are fully used,"
said Professor Klaus Cichutek, President of the Paul-Ehrlich-Institut.
Updated: 15.03.2023
