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.

This work was supported by National Institutes of Health grants AI46410 to A.L.D. and HL56416, HL67384, and DK53674 to H.E.B. A.L.D. also receives support from the Indiana Genomics Initiative (INGEN) of Indiana University. INGEN is supported in part by Lilly Endowment Inc.

We are very grateful to Mark Kaplan for the anti-Cd4 and anti-CD8 Abs. We also acknowledge Giao Hangoc for help with blood cell counts.