Professor Wilhelm Schwaeble started his scientific career in the Institute of Immunology in Munich, Germany, where he worked on the molecular characterisation of complement factor H, a regulatory component of the complement system. This project was jointly supported by Professor Elisabeth Weiss (Munich) and Professors Manfred Dierich and Thomas Schulz (Innsbruck).
He was awarded a PhD (summa cum laude) in 1988. He received an independent post-doctoral fellowship from the German Academic Exchange Council to work as a visting scientist at the MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford. In the laboratories of Dr. Robert B. Sim and Professor Kenneth B.M. Reid, he started working on another regulatory component of complement, properdin, the only complement regulator that promotes activation.
He than spent two years as an externally funded visiting research fellow at the University of Innsbruck, Austria, with Professor Manfred Dierich. From 1991 to 1993, he was appointed as research group leader at the Department of Internal Medicine to work on tumour related research projects with Professor Wolfgang Dippold.
In order to gain the necessary independence to carry out his own research programme and to attract his own research funding, he joined British Academia by appointment as a lecturer in Immunology at Leicester University to work with Professor Keith Whaley, whom Wilhelm Schwaeble met during his time in Oxford. Thanks to the excellent advice and help that he received from Dr. Robert B. Sim (Oxford) and Professor Keith Whaley, he attracted substantial research grants from the Arthritis Research Council and the Cancer Research Campaign within the first six month of his appointment to furnish and equip his laboratory in Leicester.
In Leicester, Professor Schwaeble cloned another so far unknown component of the complement system in a very fruitful collaboration with Professor Jens Jensenius¹ research group at the University of Aarhus, Denmark. This component is now termed MASP-2 (for Mannan binding lectin associated serine protease-2) and turned out to be the effector component of a novel activation pathway of complement. The lectin pathway is initiated by the recognition of carbohydrate structures present on microbial organisms via the serum lectin Mannan Binding Lectin (MBL). Very recently, three members of the ficolin family (a distinct lectin family, consisting of homopolymers of subunits, each containing both collagen-like and fibrinogen-like domains) were discovered. Like MBL, ficolins were shown to form multimolecular complexes capable of activating complement after binding to microbial carbohydrate structures using MASP-2 (the same serine protease that were first described as constituent of the MBL complex). Activation of the multimolecular MBL pathway complex (composed of up to 18 MBL monomers, the MBL-associated serine proteases MASP-1 and MASP-2, and MAp19) is initiated by the interaction of the C-terminal C-type lectin domains of MBL with carbohydrate structures present on yeasts, bacteria and viruses. This interaction is translated into activation of the complement cascade by the conversion of the MASP-2 proenzyme (it is not yet clear if and how MASP-1 participates in this process) into its enzymatically active form. The molecular architecture of the MBL/MASPs/MAp19 complex, the mechanism(s) of its activation, and the possible regulatory role of MAp19 remain to be explored in more detail. Likewise, each of the three ficolins reported to be capable of activating complement was shown to form complexes with MASP-1 and MASP-2. However, the composition, the carbohydrate specificity (two ficolins are supposed to bind N-acetylglucosamine GlcNAc), the activation sequence and regulation of complement activating ficolin complexes remain to be elucidated. As previously most antibody-independent activation of complement had been attributed to the alternative activation pathway, the discovery of the lectin route of complement activation will most likely lead to a revision of the role assigned to the alternative activation pathway of complement in innate immunity. Present results show that MASP-2 is the only lectin pathway component capable of cleaving C4 and C2 to form the classical pathway convertases C4b2a and C4b2a(C3b) required to initiate further downstream activation of complement. Thus, MASP-2 is the effector component of the lectin pathway of complement activation.
To support his work on the molecular characterization of the lectin pathway effector component MASP-2, Professor Schwaeble was awarded a 5-year programme grant by the WELLCOME TRUST. His laboratory has established very active and long-term collaborations with the research teams of Professor Jens Jensenius in Aarhus, Denmark, Professor Teizo Fujita, Fukushima Medical School, Japan, Professor Daniela Maennel, University of Regensburg, Germany, Dr. Robert B. Sim, University of Oxford, UK, Professor Eberhard Weihe, University of Marburg, Germany, and Professor Misao Matsushita, University of Tokyo, Japan.
For the success of the collaboration with the team in Japan, Professor Schwaeble's and Professor Fujita's teams were awarded the Daiwa-Adrian Prize 2001 for research excellence in Tokyo.
Professor Schwaeble is Editor-in-Chief of the Journal Immunobiology, and was recently appointed Associated Editor of the Journal of Immunology.