Understanding how normal blood-cell formation is regulated is a prerequisite for unraveling the mechanisms by which haematopoietic malignancies occur and was a major goal of the DECIDE project. The generation of blood-cells is regulated by extra-cellular signals originating from the bone marrow microenvironment. These signals include those delivered by soluble growth and/or differentiation factors, collectively called cytokines, or by direct cell contact with extra-cellular matrix molecules both of which are produced by non-hematopoietic stromal elements of the bone marrow. The precise mechanism by which these signals regulate blood-cell formation is not yet entirely understood and is the subject of intense investigation. In the DECIDE study, the role of two important bone marrow cytokines (FL and IL-7) for the generation of the antibody-secreting B cells has been investigated. Molecular and functional analyses of progenitor B-cells have led to novel insights as to the roles of these two cytokines in B cell development. It was found that rather than directly “instructing” progenitor B-cells to differentiate to mature B-cells, as had been previously hypothesized, FL and IL-7 enhanced the production of already “pre-decided” (committed) B-cell progenitors. FL made these progenitors proliferate whereas IL-7 promoted their survival, thus ensuring that sufficient B-cells were being produced by the bone marrow. Complete understanding of how extra-cellular signals regulate haematopoiesis will not only strengthen our knowledge of how cells make differentiation decisions, but will also increase the possibility of targeted therapeutic interventions in blood disorders.

PNAS paper

Lilly von MuenchowLlucia Alberti-ServeraFabian KleinGiuseppina CapoferriDaniela FinkeRhodri CeredigAntonius Rolink and Panagiotis Tsapogas Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment. Proceedings of the National Academy of Science USA. published ahead of print November 29, 2016.  doi:10.1073/pnas.1613316113

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