To find out whether the T and natural killer cells actually had come from the transplanted B cells, the researchers looked for the specific genetic footprint of B cells. Unlike most other cells in the body, B cells change their DNA sequence during their development. To produce antibodies, they bring together several gene segments by cutting and joining their DNA to create a sequence able to code for a functional antibody. The researchers found precisely this typical genetic footprint of B cells in both T cells and natural killer cells. They concluded that after the transcription factor EBF1 had been switched off, the transplanted B cells had forgotten their specialization and had turned into alternate cell types. Until now, it was only known that the absence of the transcription factor Pax5 had such an effect. "We believe that the two proteins regulate different aspects of cell type specification. EBF1 primarily represses genes that would initiate an alternative program of development in the B cells, while Pax5 ensures that they no longer react to signals that would enable them to select a different specialization," says Grosschedl.
The Freiburg-based researchers now want to understand the exact molecular interactions in the cells and better define the network of factors involved. In the long term, they hope this knowledge will allow cells to be reprogrammed, for example in the case of a pathological loss of a cell type.
|Contact: Dr. Rudolf Grosschedl|