Immune Disease Institute

The Rajewsky lab has explored how B lymphocytes develop from stem cells in the bone marrow of the mouse into mature cells and ultimately, upon contact with antigen, into memory cells. They have found that both the development and the maintenance of B cells depend on antigen receptor (BCR) expression, and they have explored the means by which B cells can somatically change BCR specificity and to which extent BCR specificity dictates the fate of the cells. In addition to a survival signal from the BCR, signals through other surface receptors are required to keep B cells alive in vivo. The nature and interplay of signals that control the homeostasis of both B and T lymphocytes in the living organism are a major focus of their research.

The main experimental approach in these studies has been gene targeting in embryonic stem (ES) cells of the mouse. Combining classical gene targeting techniques with Cre/loxP mediated site-specific recombination, the Rajewsky lab has developed a general method of targeted mutagenesis allowing the introduction of any kind of mutation into the mouse genome. This includes gene replacement as well as conditional gene targeting, i.e. targeted mutagenesis in a cell type specific and/or inducible manner.

Conditional gene targeting is ideally suited for the modeling of human diseases in mice. The group has produced numerous such mouse models, including models of various immunodeficiencies, Crohn's disease, and pulmonary fibrosis. Targeted mutagenesis of the NFkB signaling pathway has led to a mouse model of the genetic disease Incontinentia Pigmenti. Relating to this extensive earlier work on the origin of human lymphomas, in particular Hodgkin's disease (HD), they are presently heavily involved in generating mouse models of human mature B cell lymphomas.

More recently, the group begun to explore the role of microRNA control in the immune system, using gene targeting in combination with bioinformatic and proteomic approaches. This work has revealed a critical role of microRNAs in immune development and function, and microRNA control is a major focus of the present activities of the lab.

Before coming to IDI, Klaus Rajewsky was Professor of Molecular Genetics and Director at the Institute of Genetics in the University of Cologne, Germany, and the Program Coordinator of the Mouse Biology Program of the European Molecular Biology Organization (EMBO) at Monterotondo, Italy. He has received many awards and other honors, and is a member of EMBO and a foreign member of the National Academy of Sciences of the United States and Russia and the American Academy of Arts and Sciences.