Impaired Generation of Bone Marrow B Lymphocytes in Mice Deficient in C/EBPβ

Abstract

AbstractCAAT/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/EBPβ (NF-IL6) in the generation of bone marrow B lymphocytes by taking advantage of C/EBPβ−/− mice. We found that the expansion of bone marrow (BM) B lymphocytes was impaired in long-term lymphoid cultures from C/EBPβ−/− mice. Consistent with this finding, the number of BM B cells was decreased in C/EBPβ−/− mice. Both the levels of IL-7 gene expression and bioactive IL-7 from BM stromal cells were decreased in C/EBPβ−/− 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/EBPβ is required for the generation of BM B cells induced by IL-7. Accordingly, IL-7 stimulates the C/EBPβ DNA-binding activity of normal BM pre-B lymphocytes as well as of 70Z/3 pre-B cells. These results point to C/EBPβ as a critical signaling molecule in BM B lymphopoiesis.