Aberrant regulation of hematopoiesis by T cells in BAZF-deficient mice

Hal E. Broxmeyer, Sarita Sehra, Scott Cooper, Lisa M. Toney, Saritha Kusam, Jim J. Aloor, Christophe C. Marchal, Mary C. Dinauer, Alexander L. Dent

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19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5275-5285
Number of pages11
JournalMolecular and cellular biology
Volume27
Issue number15
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Broxmeyer, H. E., Sehra, S., Cooper, S., Toney, L. M., Kusam, S., Aloor, J. J., Marchal, C. C., Dinauer, M. C., & Dent, A. L. (2007). Aberrant regulation of hematopoiesis by T cells in BAZF-deficient mice. Molecular and cellular biology, 27(15), 5275-5285. https://doi.org/10.1128/MCB.01967-05