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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-11-22
pubmed:abstractText
The role of IL-7 in lymphoid development and T cell homeostasis has been extensively documented. However, the role of IL-7 in human B cell development remains unclear. We used a xenogeneic human cord blood stem cell/murine stromal cell culture to study the development of CD19+ B-lineage cells expressing the IL-7R. CD34+ cord blood stem cells were cultured on the MS-5 murine stromal cell line supplemented with human G-CSF and stem cell factor. Following an initial expansion of myeloid/monocytoid cells within the initial 2 wk, CD19+/pre-BCR- pro-B cells emerged, of which 25-50% expressed the IL-7R. FACS-purified CD19+/IL-7R+ cells were larger and, when replated on MS-5, underwent a dose-dependent proliferative response to exogenous human IL-7 (0.01-10.0 ng/ml). Furthermore, STAT5 phosphorylation was induced by the same concentrations of human IL-7. CD19+/IL-7R- cells were smaller and did not proliferate on MS-5 after stimulation with IL-7. In a search for cytokines that promote human B cell development in the cord blood stem cell/MS-5 culture, we made the unexpected finding that murine IL-7 plays a role. Murine IL-7 was detected in MS-5 supernatants by ELISA, recombinant murine IL-7 induced STAT5 phosphorylation in CD19+/IL-7R+ pro-B cells and human B-lineage acute lymphoblastic leukemias, and neutralizing anti-murine IL-7 inhibited development of CD19+ cells in the cord blood stem cell/MS-5 culture. Our results support a model wherein IL-7 transduces a replicative signal to normal human B-lineage cells that is complemented by additional stromal cell-derived signals essential for normal human B cell development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7325-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16301638-Animals, pubmed-meshheading:16301638-Antigens, CD19, pubmed-meshheading:16301638-Antigens, CD34, pubmed-meshheading:16301638-B-Lymphocytes, pubmed-meshheading:16301638-Cell Differentiation, pubmed-meshheading:16301638-Cell Lineage, pubmed-meshheading:16301638-Cell Proliferation, pubmed-meshheading:16301638-Cells, Cultured, pubmed-meshheading:16301638-Coculture Techniques, pubmed-meshheading:16301638-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:16301638-Flow Cytometry, pubmed-meshheading:16301638-Hematopoietic Stem Cells, pubmed-meshheading:16301638-Humans, pubmed-meshheading:16301638-Interleukin-7, pubmed-meshheading:16301638-Mice, pubmed-meshheading:16301638-Models, Immunological, pubmed-meshheading:16301638-Phosphorylation, pubmed-meshheading:16301638-Receptors, Interleukin-7, pubmed-meshheading:16301638-STAT5 Transcription Factor, pubmed-meshheading:16301638-Stromal Cells
pubmed:year
2005
pubmed:articleTitle
Murine and human IL-7 activate STAT5 and induce proliferation of normal human pro-B cells.
pubmed:affiliation
The Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural