The development of the adaptive immune system is a highly dynamic and complex process. The molecular mechanisms guiding this process have not yet been fully unraveled. The major aims of projects described in this application are to obtain a better understanding of the cellular and molecular mechanisms that orchestrate the normal development of lymphocytes. Various human diseases such as leukemia’s and lymphomas, autoimmune diseases and immunodeficiency syndromes are, at least in part, due to abnormalities in this developmental process. Therefore, a better understanding of normal lymphocyte development might help to elucidate the molecular mechanisms underlying these diseases.

In our projects we will especially emphasize the interplay between IL-7 and FLT3L, two cytokines that play a crucial role in early hematopoietic development. Therefore, mice deficient for these cytokines and/or over-expressing these will be generated and analyzed in detail.  Moreover, we will try to unravel the role of the transcription factor Duxbl in hematopoietic development. Initial experiments showed that Duxbl over-expression in the hematopoietic system leads to a severe block in T cell development in the thymus and B cell development in bone marrow. These findings suggest that this transcription factor plays a crucial previously not yet appreciated role in early lymphocyte development.