Aberrant regulation of hematopoiesis by T cells in BAZF-deficient mice.
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.
Broxmeyer
Hal E
HE
Department of Microbiology and Immunology and The Walther Oncology Center, 950 W. Walnut St. R2 302, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Sehra
Sarita
S
Cooper
Scott
S
Toney
Lisa M
LM
Kusam
Saritha
S
Aloor
Jim J
JJ
Marchal
Christophe C
CC
Dinauer
Mary C
MC
Dent
Alexander L
AL
D000818:Animals; D001772:Blood Cell Count; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D018925:Chemokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000172:deficiency; D006410:Hematopoiesis / Q000187:drug effects; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D022423:Myeloid Cells / Q000187:drug effects; D010641:Phenotype; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism
C490010:Bcl6 protein, mouse; C113027:Bcl6b protein, mouse; D018925:Chemokines; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D019089:Stem Cell Factor