Control of hematopoietic cell differentiation by c-Fos and Bcl6

点击翻译按钮获取中文摘要

Proliferation and differentiation of hematologic cells are regulated by transcriptional factors. We have analyzed role of two immediated early genes, c-Fos and Bcl6.c-Fos forms AP-1 complex with Jun family and regulates the expression of AP-1 binding genes. Expression of c-fos is induced in normal myelopoiesis. To explore the function of c-fos on myeloid differentiation, we used the murine myeloblastic leukemia cell line M1. Stimulation of M1 cells with LPS promotes their terminal differentiation into functional macrophages. Overexpression of c-fos in M1 cells dramatically increased sensitivity of the cells for LPS-induced differentiation and generation of morphologically differentiated cells. However, the overexpression did not modulate phagocytotic functions, surface expression of macrophage markers such as CD16/CD32 (FcgR) and CD54 (ICAM-1), and expression of lysozyme, esterase and c-fins mRNA. Induction of the class II MHC expression on M1 cells after stimulation was inhibited by t … More he overexpression. Expression of CIITA was also reduced in the M1 cells. Overexpression of c-fos in differentiating M1 cells perturbs their functional maturation.The Bcl6 gene has been identified from the chromosomal translocation breakpoint in B-cell lymphoma and its product functions as a sequence-specific transcriptional repressor. After immunization with T cell-dependent antigens, the high-affinity B cells selected in germinal centers differentiate into memory B cells or long-lived antibody forming cells. We showed that Bcl6-deficient B cells, which cannot develop germinal centers, differentiated into IgM and IgG1 memory B cells but barely into long-lived IgG1 antibody forming cells in the bone marrow. Mutation in the V-heavy gene was nil in these memory B cells. Bcl6 and germinal center formation are essential for somatic hypermutation and affinity maturation, and generation of memory B cells can occur independent of germinal center formation, Ig class-switching and affinity maturation. Less