title: Modulation of IL-7 thresholds by SOCS proteins in developing B lineage cells.
abstract: During B lymphopoiesis, IL-7 induces survival, proliferation, and differentiation signals that are important during the pro-B to pre-B cell transition. We showed that murine small pre-B stage cells do not signal or proliferate in response to IL-7, yet they maintain IL-7R surface expression. Loss of proliferative responsiveness to IL-7 is mediated by suppressor of cytokine signaling protein 1 (SOCS-1), the expression of which is regulated during B lymphopoiesis, with the highest levels observed in small pre-B cells. SOCS-1 inhibits IL-7 responses in pre-B cell lines and ex vivo B lineage cells. SOCS-1 expression and, thus, responsiveness to IL-7, can be regulated by IL-7 itself, as well as IFN-γ and IL-21. Additionally, the transcriptional repressor Gfi-1b enhances the proliferative responsiveness of B cell lines to IL-7. We demonstrated that these molecules act together to form a SOCS-mediated "rheostat" that controls the level of IL-7R signaling in developing murine B lineage cells.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2M9, Canada. steve.corfe@utoronto.ca
authors.forename: Steven A
authors.initials: SA
authors.lastname: Corfe
authors.forename: Robert
authors.initials: R
authors.lastname: Rottapel
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Paige
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D050826:Suppressor of Cytokine Signaling Proteins