Institute for Immunology and Transfusion Medicine , University of Greifswald
I studied biochemistry in Edinburgh before moving to the LMB in Cambridge for my Ph.D. which involved protein sequencing. At the end of my three years I knew I never wanted to sequence another protein ever again. However, when applying for Post.Doc. positions in all sorts of interesting labs, everyone seemed to have a protein at the back of their freezer which needed to be sequenced. In desperation I asked Cesar Milstein if he didn’t know someone who either lacked a freezer or at least was unlikely to have a protein hidden in it. He suggested I try Klaus Rajewsky in Cologne. Klaus had freezers but, thank God, no interest in sequencing any proteins. The stay in Cologne was my introduction to immunology and to developmental biology, which I followed up by moving to Walter Gehring’s group in the Biozentrum in Basel. For many years Drosophila genetics, in particular gene control by sequence specific DNA binding proteins was in the center of my interest.
However, I returned to immunology when I moved to Greifswald. There - with lots of help from the Rajewsky lab – I established the generation of knock out mice and applied this technique to the analysis of macrophage activation. We generated the LBP deficient mouse to study macrophage interaction with LPS and the IL10R1alpha knock out to study the activation of peritoneal macrophages. I retired four years ago but remain fascinated by the subtlety and complexity of the immune system.
Institute for Pathology, Julius-Maximilians-University, Würzburg
Deutsches Rheuma-Forschungszentrum Berlin
Instiute of Transplant Immunology, Medical School Hannover
Institut für Medizinische Mikrobiologie and Krankhaushygiene, Marburg
I started my career by studying mathematics and physics to become a teacher. However, then I was thrown into civil service and drove an ambulance car which changed my perception of life and convinced me, to reject my own concerns and indeed study medicine, which I did in Würzburg. Here I noted that logics of mathematics was not an acceptable wish and professors continuously told me not to ask why something would be as it is, but rather accept it as general experience. This brought me a real crisis, until I met Eberhard Wecker, the father of the first cytokine to be described, who "explained" me virology. Therefter, I mainly studied as a side approach and mostly worked for my MD thesis in his lab under supervision of Anneliese Schimpl (the mother of this cytokine) to create the second hybrid monoclonal antibody (Milstein was faster).
After my examination, I was lucky to be traced towards Martin Röllinghoff in Erlangen, who taught me how well suited the German scientific landscape was for an MD to combine specialisation in Microbiology and research in Immunology. This decided my personal career. After completing my training as microbiologist and a research stay in the lab of Tak Mak in Toronto, I eventually accepted the chair position for Medical Microbiology in Marburg. In research, I have always been involved in T cell subset differentiation and the role of IRF transcription factors in this process. Immunology has always been my fascination and I have served the DGfI as my "home society", by establishing (together with others) the Ettal school, by founding and leading for about 20 years the research focus group on T cells, and finally by working as president of this society.
Deutsches Rheuma-Forschungszentrum Berlin
Fritz Melchers obtained a diploma in chemistry (dipl.chem.) in 1961, and a Ph.D. (Dr. rer.nat.) in 1964 in biochemistry and genetics (Dr. Hans-Georg Zachau) on the structure of serine-t-RNA at the University of Cologne. After three years of postdoctoral work at the Salk Institute in La Jolla, California, working in the laboratory of Dr. Edwin S. Lennox on antibody synthesis and secretion in mouse plasmacytomas, he started his own research group at the Max Planck Institute for Molecular Genetics, headed by Professor Thomas Trautner, continuing the work on antobody synthesis and secretion and the role of carbohydrate attachments in these processes. He also studied the interactions of antibodies with the enzyme betagalactosidase. In 1971, after short research activities at the Weizmann Institute in Rehovot, Israel (Professor Michael Sela, Antibodies against carbohydrate portions of antibodies) and Stanford University (Professor Len Herzenberg, FACS development, B cell sorting), he joined the Basel Institute for Immunology (Director Professor Niels Kaj Jerne) in Basel, Switzerland as Permanent Scientific Member. With Dr. Jan Andersson and other members he studied antibody synthesis, surface deposition, turnover and secretion, now also in resting, mature splenic B-cells and in mitogen (LPS, lipoprotein) activated B-cell, plasmablasts and plasma cells. With Dr. Robert Phillips he included in these studies antibody synthesis and mitogen reactivity in fetal liver-derived preB-cells, which later, in work together with Nobuo Sakaguchi. Akira Kudo. Hajime Karasuyama, Kazuo Ohnishi and others led to the discovery of VpreB and lambda5, forming the surrogate light chain. This initiated studies on the structure and function of the preB-cell receptor, which is formed with IgH-chains in preB cells. These studies have continued until recently. With Dr. Ton Rolink he developed ways to analyse B-cell development from early progenitors to plasma cells. The discovery, that preB-cells can be grow and cloned in tissue cultures with preadipocytic stromal cells and IL7, and that such cell lines could also be established from PAX5-deficient bone marrow progenitors have been the basis for many studies “in vitro”, and after transplantation “in vivo” to detail cellular stages and molecular steps of B-cell development. Twenty years after Fritz Melchers had succeded Niels Jerne as director in 1981 the Basel Institute for Immunology closed in 2001, coincident with his retirement. In 2004 he started a Senior Research Group on “Lymphocyte development” at the Max Planck Institute for Infection Biology, where he continued his studies on the role of the preB-cell receptor in B-cell development, and began to follw the development of HSC, early progenitors and B-cells during embryonic development of the mouse, also from ES cells and iPS cells, and the flexibilities, potencies and restrictions imposed by their “in vivo” environments. In 2017 he moved his “Lymphocyte development” group to the DRFZ.
A biologist by education, I graduated at the Genetics Institute of the Cologne University, Germany, mentored by Klaus Rajewsky. I later became Associate Professor there and was a visiting scientist with Max Cooper and John Kearney at the University of Alabama. Since 1996, I am the Scientific Director of the German Rheumatism Research Center in Berlin, a Leibniz Institute, and Professor at the Charité Medical Center in Berlin.
My research aims at understanding the lifestyle of lymphocytes, in particular the successful ones that confer immunological memory and the loosers that drive chronic immune reactions. My group uses cytometric technologies to observe and isolate individual lymphocytes in vivo and ex vivo. In this context we developed the MACS technology. From the original observation that antibody-class switching in individual B lymphocytes is targeted to distinct classes by distinct cytokines, I got curious how cytokine gene expression in T lymphocytes is induced and memorized. We first developed the intracellular cytokine staining and the cytometric secretion assay technologies to analyse the expression of cytokines by individual cells. Then we could analyse how T cells get instructed by IL-4 and IL-12 to become Th2 and Th1 cells, respectively, and how this instruction is memorized by epigenetic imprinting of the cytokine genes. Originally a side track, we used the cytometric secretion assay also to track antibody secreting plasma cells in vivo. This led to the fundamental discovery of longlived memory plasma cells, maintained in dedicated survival niches organized by stromal cells. Many of them reside in the bone marrow. We then could show that also memory T and B lymphocytes reside and rest in the bone, challenging current paradigms, and this discussion is not yet finished. With respect to the loosers, memory plasma cells secreting pathogenic autoantibodies obviously can drive chronic immune reactions. They require novel therapeutic strategies, since in their niches they are refractory to conventional immunosuppression. Recently, we could identify also pathogenic T lymphocytes, not only able to induce, but also driving chronic inflammation. They express genes like Twist1, adapting their function, metabolism and survival to chronicity, and also making them refractory to conventional immunosuppression, a challenge that we are addressing now. Thus the cell-centered perspective on immune-mediated diseases offers entirely new options for their therapy, and the promise of therapy-free remission.
Rheumaeinheit Med. Poliklinik, Klinikum der Universität München