BLIMP-I: trigger for differentiation of myeloid lineage

B lymphocyte-induced maturation protein-1 (BLIMP-1 or PRDI-BF1) is induced when bone marrow-derived progenitors differentiate in response to macrophag e-colony stimulating factor (M-CSF) and is present in peripheral blood mono cytes and granulocytes. BLIMP-1 is also induced during differentiation of U 937 and HL-60 cells into macrophages or granulocytes. Induction of BLIMP-1 mRNA during macrophage differentiation of U937 and HL-60 shows a biphasic p attern. Overexpression of BLIMP-1 is sufficient to initiate macrophage diff erentiation of U937 cells whereas blocking endogenous BLIMP-1 inhibits diff erentiation. One target of BLIMP-1-dependent transcriptional repression in U937 cells is c-myc, providing an explanation for cessation of cell divisio n. Thus BLIMP-1 is a key regulator of terminal differentiation in two separ ate hematopoietic lineages: myeloid cells and B lymphocytes.