Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 283K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nakamura, K. Articles by Coggeshall, K. M. Search for Related Content PubMed PubMed Citation Articles by Nakamura, K. Articles by Coggeshall, K. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Social Bookmarking                            What's this?

¹ Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104
² Department of Microbiology and Immunology, University of Oklahoma, Oklahoma City, OK 73104
³ Department of Cell Biology, University of Oklahoma, Oklahoma City, OK 73104

Address correspondence to K. Mark Coggeshall, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104. Phone: (405) 271-7209; Fax: (405) 271-8569; email: mark-coggeshall{at}omrf.ouhsc.edu

The Src homology (SH)2–containing inositol 5-phosphatase (SHIP) negatively regulates a variety of immune responses through inhibitory immune receptors. In SHIP^-/- animals, we found that the number of early lymphoid progenitors in the bone marrow was significantly reduced and accompanied by expansion of myeloid cells. We exploited an in vitro system using hematopoietic progenitors that reproduced the in vivo phenotype of SHIP^-/- mice. Lineage-negative marrow (Lin^-) cells isolated from wild-type mice failed to differentiate into B cells when cocultured with those of SHIP^-/- mice. Furthermore, culture supernatants of SHIP^-/- Lin^- cells suppressed the B lineage expansion of wild-type lineage-negative cells, suggesting the presence of a suppressive cytokine. SHIP^-/- Lin^- cells contained more IL-6 transcripts than wild-type Lin^- cells, and neutralizing anti–IL-6 antibody rescued the B lineage expansion suppressed by the supernatants of SHIP^-/- Lin^- cells. Finally, we found that addition of recombinant IL-6 to cultures of wild-type Lin^- bone marrow cells reproduced the phenotype of SHIP^-/- bone marrow cultures: suppression of B cell development and expansion of myeloid cells. The results identify IL-6 as an important regulatory cytokine that can suppress B lineage differentiation and drive excessive myeloid development in bone marrow.

Key Words: lymphopoiesis • inflammation • SHIP • interleukin 6

Abbreviations used in this paper: FcRII, Fc receptor II; NOD, nonobese diabetic; PI-3K, phosphatidylinositol 3-kinase; PIP3, phosphatidylinositol 3,4,5-trisphosphate; SH, src homology; SHIP, SH2-containing 5-inositol phosphatase.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Costinean, S., Sandhu, S. K., Pedersen, I. M., Tili, E., Trotta, R., Perrotti, D., Ciarlariello, D., Neviani, P., Harb, J., Kauffman, L. R., Shidham, A., Croce, C. M. (2009). Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein {beta} are targeted by miR-155 in B cells of E{micro}-MiR-155 transgenic mice. Blood 114: 1374-1382 [Abstract] [Full Text]  
• Haddon, D. J., Antignano, F., Hughes, M. R., Blanchet, M.-R., Zbytnuik, L., Krystal, G., McNagny, K. M. (2009). SHIP1 Is a Repressor of Mast Cell Hyperplasia, Cytokine Production, and Allergic Inflammation In Vivo. J. Immunol. 183: 228-236 [Abstract] [Full Text]  
• Maeda, K., Malykhin, A., Teague-Weber, B. N., Sun, X.-H., Farris, A. D., Coggeshall, K. M. (2009). Interleukin-6 aborts lymphopoiesis and elevates production of myeloid cells in systemic lupus erythematosus-prone B6.Sle1.Yaa animals. Blood 113: 4534-4540 [Abstract] [Full Text]  
• Minami, A., Tsuboi, I., Harada, T., Fukumoto, T., Hiramoto, M., Koshinaga, M., Hirabayashi, Y., Kanno, J., Inoue, T., Aizawa, S. (2007). Inflammatory Biomarker, Neopterin, Suppresses B Lymphopoiesis for Possible Facilitation of Granulocyte Responses, Which Is Severely Altered in Age-Related Stromal-Cell-Impaired Mice, SCI/SAM. Exp. Biol. Med. 232: 134-145 [Abstract] [Full Text]  
• Igarashi, H., Baba, Y., Nagai, Y., Jimi, E., Ghosh, S., Kincade, P. W (2006). NF-{kappa}B is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNF{alpha}. Int Immunol 18: 653-659 [Abstract] [Full Text]  
• Maeda, K., Baba, Y., Nagai, Y., Miyazaki, K., Malykhin, A., Nakamura, K., Kincade, P. W., Sakaguchi, N., Coggeshall, K. M. (2005). IL-6 blocks a discrete early step in lymphopoiesis. Blood 106: 879-885 [Abstract] [Full Text]  
• Vedham, V., Phee, H., Coggeshall, K. M. (2005). Vav Activation and Function as a Rac Guanine Nucleotide Exchange Factor in Macrophage Colony-Stimulating Factor-Induced Macrophage Chemotaxis. Mol. Cell. Biol. 25: 4211-4220 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS