Aberrant Regulation of Hematopoiesis by T Cells in BAZF-Deficient Mice

Abstract

The BAZF (BCL-6b) protein is highly similar to the BCL-6 transcriptional repressor. While BCL-6 has been characterized extensively, relatively little is known about the normal function of BAZF. In order to understand the physiological role of BAZF, we created BAZF-deficient mice. Unlike BCL-6-deficient mice, BAZF-deficient mice are healthy and normal in size. However, BAZF-deficient mice have a hematopoietic progenitor phenotype that is almost identical to that of BCL-6-deficient mice. Compared to wild-type mice, both BAZF-deficient and BCL-6-deficient mice have greatly reduced numbers of cycling hematopoietic progenitor cells (HPC) in the BM and greatly increased numbers of cycling HPC in the spleen. In contrast to HPC from wild-type mice, HPC from BAZF-deficient and BCL-6-deficient mice are resistant to chemokine-induced myelosuppression and do not show a synergistic growth response to granulocyte-macrophage colony-stimulating factor plus stem cell factor. Depletion of CD8 T cells in BAZF-deficient mice reverses several of the hematopoietic defects in these mice. Since both BAZF- and BCL-6-deficient mice have defects in CD8 T-cell differentiation, we hypothesize that both BCL-6 and BAZF regulate HPC homeostasis by an indirect pathway involving CD8 T cells.

Role of SOX17 in hematopoietic development from human embryonic stem cells

“…These genes have been implicated in vasculogenesis and/or angiogenesis and BAZF/BCL6B and JUNB have also been implicated in hematopoiesis. [30][31][32][33][34] The profiles of these Sox17 targets during early hematopoietic development further support the critical role of SOX17 in the regulation of HE.…”

BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signaling in angiogenesis

“…It has been reported that BAZF Ϫ/Ϫ mice are viable, healthy, and normal in size. 22,33 Vasculogenesis and angiogenesis abnormalities in BAZF Ϫ/Ϫ mice have not been reported. However, close examination of the retinas of mice with gene disruption of BAZF showed reduction in vascular density and sprouts in the peripheral part of the developing retinal vascular plexus at P5 ( Figure 5A-E, supplemental Figure 6A).…”

Kaposi's Sarcoma-Associated Herpesvirus Encodes an Ortholog of miR-155

“…Bim is required for the apoptosis of activated T cells following viral infection, which is critical for limiting antiviral immune responses (50). BAZF is required for secondary responses of memory CD8 ϩ T cells (40) and was recently linked to the homeostasis of hematopoietic progenitors (7). Thus, the observed down-regulation of these genes by miR-155 or miR-K12-11 suggests important roles in the regulation of immune responses to infection as well as in targeting apoptosis to regulate cell survival during lymphocyte differentiation.…”