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BLIMP-1: trigger for differentiation of myeloid lineage

Abstract

B lymphocyte–induced maturation protein-1 (BLIMP-1 or PRDI-BF1) is induced when bone marrow–derived progenitors differentiate in response to macrophage–colony stimulating factor (M-CSF) and is present in peripheral blood monocytes and granulocytes. BLIMP-1 is also induced during differentiation of U937 and HL-60 cells into macrophages or granulocytes. Induction of BLIMP-1 mRNA during macrophage differentiation of U937 and HL-60 shows a biphasic pattern. Overexpression of BLIMP-1 is sufficient to initiate macrophage differentiation of U937 cells whereas blocking endogenous BLIMP-1 inhibits differentiation. One target of BLIMP-1–dependent transcriptional repression in U937 cells is c-myc, providing an explanation for cessation of cell division. Thus BLIMP-1 is a key regulator of terminal differentiation in two separate hematopoietic lineages: myeloid cells and B lymphocytes.

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Figure 1: BLIMP-1 mRNA is expressed in human peripheral blood monocytes and granulocytes, and induced during differentiation of primary murine macrophages.
Figure 2: BLIMP-1 expression is induced in U937 and HL-60 cells treated with PMA, and in HL-60 cells treated with DMSO.
Figure 4: T-BLIMP delays or inhibits the expression macrophage-specific surface proteins CD11b and CD11c, and impairs the phagocytotic ability of PMA-treated U937 cells.
Figure 3: U937 stable transfectants expressing T-BLIMP.
Figure 5: BLIMP-1 expression is sufficient to drive macrophage differentiation of U937 cells.
Figure 6: c-myc is a target of BLIMP-1 repression during U937 differentiation.

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Acknowledgements

We thank R. Dalla-Favera, S. Greenberg, C. Schindler, S. Silverstein and K.-I. Lin for reading the manuscript and for discussions, D.J. Husemann and J. Rooney for discussions and technical advice, G. Cattoretti for technical support. We are grateful to members of the Calame laboratory especially J. Liao for technical assistance and J. Yu for providing the T-BLIMP construct. Supported by National Institutes of Health Cancer Biology Training grant 2 T32 CA09503-14 (to D.H.C) and RO1-AI43576 (to K.C).

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Correspondence to Kathryn Calame.

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Chang, D., Angelin-Duclos, C. & Calame, K. BLIMP-1: trigger for differentiation of myeloid lineage. Nat Immunol 1, 169–176 (2000). https://doi.org/10.1038/77861

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