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.
● Lilly von Muenchow, Llucia Alberti-Servera, Fabian Klein, Giuseppina Capoferri, Daniela Finke, Rhodri Ceredig, Antonius 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