Stat-1 is not essential for inhibition of B lymphopoiesis by type I IFNs.
Type I IFNs, IFN-alpha, -beta, and -omega, are cytokine family members with multiple immune response roles, including the promotion of cell growth and differentiation. Conversely, the type I IFNs are potent inhibitors of IL-7-dependent growth of early B lineage progenitors, effectively aborting further B lineage differentiation at the pro-B cell stage. Type I IFNs alpha and beta function via receptor-mediated activation of a Jak/Stat signaling pathway in which Stat-1 is functionally important, because many IFN-induced responses are abrogated in Stat-1-deficient mice. To the contrary, we show here that the inhibition of IL-7-dependent B lymphopoiesis by IFN-alphabeta is unaffected in Stat-1-deficient mice. The present data indicate that the type I IFNs can activate an alternative signaling pathway in which neither Stat-1 nor phosphatidylinositol 3'-kinase are essential components.
Gongora
R
R
Division of Developmental and Clinical Immunology, Department of Medicine, University of Alabama, Birmingham, AL 35294, USA.
Stephan
R P
RP
Schreiber
R D
RD
Cooper
M D
MD
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D005260:Female; D006131:Growth Inhibitors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D007370:Interferon Type I / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D007370:Interferon Type I; D015851:Interleukin-7; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D019869:Phosphatidylinositol 3-Kinases