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Developmental stage-specific effects of Pim-1 dysregulation on murine bone marrow B cell development
- Source :
- BMC Immunology
- Publisher :
- Springer Nature
-
Abstract
- Background The serine threonine kinase Pim-1 has documented roles in hematopoietic progenitor and B cell precursor proliferation and survival. Pim-1 is a molecular target of the transcription factor Hoxa9. Previous studies showed that Pim-1 deficiency phenocopied the hematopoietic progenitor defect in hoxa9-/- mice and forced expression of Pim-1 normalized the in vitro proliferation defect inherent to hoxa9-/- hematopoietic progenitors. Pim-1 is induced by cytokine signaling, including the early lymphoid/B lineage regulators Flt3 and IL-7, and expression levels were shown to influence the size of the B cell compartment in bone marrow (BM). Results In this study, we sought to determine if transgenic expression of Pim-1, driven by the immunoglobulin enhancer, Eμ, was sufficient to rescue the lymphoid/B cell precursor defect in hoxa9 or flt3-ligand (flt3l) deficient mice. Unexpectedly, expression of Eμ − Pim1 exacerbated lymphoid progenitor deficiencies in flt3l-/-, and to a lesser extent, hoxa9-/- mice. Furthermore, Eμ − Pim1 expression alone reduced early myeloid and lymphoid, but not erythroid, progenitors. In contrast, Pim-1 deficiency had no significant effect on early lymphoid/B cell development through the Pre-Pro-B cell stage, but caused a significant reduction in IgM− B cell precursors. Importantly, loss of Pim-1 did not phenocopy hoxa9- or flt3l-deficiency on the lymphoid/early B cell progenitor pools. Conclusions These experimental findings demonstrate that Pim-1 overexpression has developmental-stage-specific effects on B lymphopoiesis and myelopoiesis. Importantly, these suggest that Pim-1 deficiency does not contribute significantly to the early lymphoid/B cell developmental deficiency in hoxa9-/- or flt3l-/- mice.
- Subjects :
- 0301 basic medicine
Myeloid
Eμ-Pim1 transgene
Cell Survival
Cellular differentiation
Immunology
PIM1
Bone Marrow Cells
Mice, Transgenic
Biology
03 medical and health sciences
Mice
Proto-Oncogene Proteins c-pim-1
hemic and lymphatic diseases
B cell development
medicine
Animals
Hoxa9
Cell Lineage
Lymphopoiesis
Transgenes
Progenitor cell
Flt3
B cell
Cells, Cultured
Cell Proliferation
Homeodomain Proteins
Mice, Knockout
B-Lymphocytes
Cell growth
Precursor Cells, B-Lymphoid
Cell Differentiation
pim1
B cell precursors
Hematopoiesis
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
fms-Like Tyrosine Kinase 3
Cancer research
Myelopoiesis
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 14712172
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Immunology
- Accession number :
- edsair.doi.dedup.....7928a276453112b34ae84bca1142567c
- Full Text :
- https://doi.org/10.1186/s12865-016-0152-1