Knock Knock Knock, Who is there? - Cell Crosstalk within the Bone Marrow

Abstract: This thesis is focused on the subject of cell-cell interaction. Our body is composed of cells, most of them are integrated in a network with other cells that together forms tissues and organs. Every cell type in these complex organs has its special task and location. This is true whether we are doing research on humans or, as we have been, investigating mice. Mice are excellent models for studies of blood cell development since this process in mice resembles human blood cell generation in many regards.Cells communicate with each other by sending out small molecules or by directly binding to surrounding cells; to cells of the same kind as well as to cells with different origins and tasks. A cell is surrounded by hundreds of different signal-carrying entities; soluble, bound to the extra cellular matrix or bound to its surface. Every cell has to distinguish and respond to the environment according to its own specific nature.In the first article interleukin 7 (IL-7) a growth factor expressed by the stroma cells was studied. Results show that IL-7 is crucial for the immature progenitor cell in its development towards antibody producing B-lymphocytes. The second article is about stroma cells and their ability to support the development of B-cells. It is a comparative study on two different cell lines, where we focus on transcription factors and their regulation of protein induction of factors supporting B-cells. This study increased our knowledge of stroma cells. In the third paper we combined our knowledge from the first two papers in regard to stroma cells as well as B-cell development by testing if there is a possibility to theoretically find new factors of importance for the maturing B-cell. We achieved this by the development of GCINT, a database investigating possible receptorligand interactions between two cells, verifying these results in vitro with cell lines as well as primary cells. This revealed a two way communication between blood cells and stroma cells, highlighting the complexity of the bone marrow environment. In the last article we continued this work with primary FACS sorted stroma cells investing the potential connections between each of the stroma cell populations with primary blood cells in different stages of development. This work supports a model where hematopoietic cells can interact with stroma cells in a stage-specific manner and that the exchange between cells is of importance for their maturation.