Abstract
During early stages of B-lineage differentiation in bone marrow, signals emanating from IL-7R and pre-BCR are thought to synergistically induce proliferative expansion of progenitor cells. Paradoxically, loss of pre-BCR-signaling components is associated with leukemia in both mice and humans. Exactly how progenitor B cells perform the task of balancing proliferative burst dependent on IL-7 with the termination of IL-7 signals and the initiation of L chain gene rearrangement remains to be elucidated. In this article, we provide genetic and functional evidence that the cessation of the IL-7 response of pre-B cells is controlled via a cell-autonomous mechanism that operates at a discrete developmental transition inside Fraction C' (large pre-BII) marked by transient expression of c-Myc. Our data indicate that pre-BCR cooperates with IL-7R in expanding the pre-B cell pool, but it is also critical to control the differentiation program shutting off the c-Myc gene in large pre-B cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism*
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B-Lymphocyte Subsets / pathology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Line
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Cells, Cultured
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Coculture Techniques
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Gene Knock-In Techniques
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / genetics
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Interleukin-7 / antagonists & inhibitors
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Interleukin-7 / metabolism
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Interleukin-7 / physiology*
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Mice
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Mice, Knockout
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Proto-Oncogene Proteins c-myc / biosynthesis
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Proto-Oncogene Proteins c-myc / genetics*
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Receptors, Interleukin-7 / antagonists & inhibitors
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Receptors, Interleukin-7 / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology
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Stem Cells / immunology*
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Stem Cells / metabolism*
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Stem Cells / pathology
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Stromal Cells / immunology
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Stromal Cells / metabolism
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Stromal Cells / pathology
Substances
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Growth Inhibitors
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Interleukin-7
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Proto-Oncogene Proteins c-myc
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Receptors, Interleukin-7