Impaired generation of bone marrow B lymphocytes in mice deficient in C/EBPbeta.
CAAT/enhancer binding proteins (C/EBP) are a family of transcription factors that mediates adipocyte differentiation and the regulation of genes expressed in immune responses and inflammation, such as interleukin-6 (IL-6), IL-8, and granulocyte colony-stimulating factor (G-CSF). We investigated the role of C/EBPbeta (NF-IL6) in the generation of bone marrow B lymphocytes by taking advantage of C/EBPbeta-/- mice. We found that the expansion of bone marrow (BM) B lymphocytes was impaired in long-term lymphoid cultures from C/EBPbeta-/- mice. Consistent with this finding, the number of BM B cells was decreased in C/EBPbeta-/- mice. Both the levels of IL-7 gene expression and bioactive IL-7 from BM stromal cells were decreased in C/EBPbeta-/- mice. Furthermore, the proliferative responsiveness of BM B-cell precursors to IL-7 was also reduced as compared to wild-type mice, indicating that C/EBPbeta is required for the generation of BM B cells induced by IL-7. Accordingly, IL-7 stimulates the C/EBPbeta DNA-binding activity of normal BM pre-B lymphocytes as well as of 70Z/3 pre-B cells. These results point to C/EBPbeta as a critical signaling molecule in BM B lymphopoiesis.
Chen
X
X
Dipartimento di Medicina Sperimentale e Clinica, Università di Reggio Calabria, Catanzaro, Italy.
Liu
W
W
Ambrosino
C
C
Ruocco
M R
MR
Poli
V
V
Romani
L
L
Quinto
I
I
Barbieri
S
S
Holmes
K L
KL
Venuta
S
S
Scala
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D022762:CCAAT-Enhancer-Binding Proteins; D002452:Cell Count; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D015851:Interleukin-7 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015851:Interleukin-7; D009687:Nuclear Proteins