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Impaired Generation of Bone Marrow B Lymphocytes in Mice Deficient in C/EBP
Xueni Chen,
Weimin Liu,
Concetta Ambrosino,
Maria R. Ruocco,
Valeria Poli,
Luigina Romani,
Ileana Quinto,
Susan Barbieri,
Kevin L. Holmes,
Salvatore Venuta, and
Giuseppe Scala
From the Dipartimento di Medicina Sperimentale e Clinica, Università di Reggio Calabria, Catanzaro, Italy; Dipartimento di Biochimica e Biotecnologie Mediche, Università "Federico II," Napoli, Italy; Istituto di Ricerche di Biologia Molecolare P. Angeletti, (IRBM) Pomezia, Roma, Italy; Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Perugia, Perugia, Italy; and Laboratory of Molecular Structure and Laboratory of Immunopathology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD.
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/EBP (NF-IL6) in the generation of bone marrow B lymphocytes by taking advantage of C/EBP-/- mice. We found that the expansion of bone marrow (BM) B lymphocytes was impaired in long-term lymphoid cultures from C/EBP-/- mice. Consistent with this finding, the number of BM B cells was decreased in C/EBP-/- mice. Both the levels of IL-7 gene expression and bioactive IL-7 from BM stromal cells were decreased in C/EBP-/- 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/EBP is required for the generation of BM B cells induced by IL-7. Accordingly, IL-7 stimulates the C/EBP DNA-binding activity of normal BM pre-B lymphocytes as well as of 70Z/3 pre-B cells. These results point to C/EBP as a critical signaling molecule in BM B lymphopoiesis.
Blood, Vol. 90 No. 1 (July 1), 1997:
pp. 156-164
© 1997 by The American Society of Hematology.
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