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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells
Branko Cirovic1, Jörg Schönheit2, Elisabeth Kowenz-Leutz2
1Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany; Humboldt-University of Berlin, Institute of Biology, 10115 Berlin, Germany.
Abstract:
The lymphoid-myeloid transdifferentiation potentials of members of the C/EBP family (C/EBPα, β, δ, and ε) were compared in v-Abl-immortalized primary B cells. Conversion of B cells to macrophages was readily induced by the ectopic expression of any C/EBP, and enhanced by endogenous C/EBPα and β activation. High transgene expression of C/EBPβ or C/EBPε, but not of C/EBPα or C/EBPδ, also induced the formation of granulocytes. Granulocytes and macrophages emerged in a mutually exclusive manner. C/EBPβ-expressing B cells produced granulocyte-macrophage progenitor (GMP)-like progenitors when subjected to selective pressure to eliminate lymphoid cells. The GMP-like progenitors remained self-renewing and cytokine-independent, and continuously produced macrophages and granulocytes. In addition to their suitability to study myelomonocytic lineage bifurcation, lineage-switched GMP-like progenitors could reflect the features of the lympho-myeloid lineage switch observed in leukemic progression.
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