IFN-gamma abrogates IL-7-dependent proliferation in pre-B cells, coinciding with onset of apoptosis.
These studies investigated the mechanism by which interferon-gamma (IFN-gamma) inhibits the interleukin-7 (IL-7)-dependent proliferation of BALB/c bone marrow B-cell precursors in vitro. Low concentrations (1 U/ml) of recombinant murine IFN-gamma (rmIFN-gamma) caused a approximately 80% suppression of IL-7 colony-forming units (CFU) formation in semi-solid media, in part through a direct affect on isolated B220+ pre-B cells. IFN-gamma did not induce apoptosis in small resting pre-B cells in BALB/c bone marrow. There was no difference in the proportion of apoptotic B220+ pre-B cells in IFN-gamma-treated cultures compared to cultures treated with IL-7 alone. However, IL-7-responsive pre-B cells generated from bone marrow had a 30-50% loss in cells in S+G2/M phases of the cell cycle and an increase of up to twice as many in apoptotic cells within 48 hr of exposure to IFN-gamma. Notably, expression of the tyrosine phosphatase B220 was increased in the IFN-gamma-treated pre-B cells. Interestingly, although there was no substantial change in IL-7 receptor mRNA expression upon IFN-gamma treatment, a small decrease in binding of biotinylated IL-7 to IFN-gamma-treated pre-B cells was observed. These results suggest that IFN-gamma inhibits IL-7 responsiveness in pre-B cells, resulting in a subtle down-regulation of IL-7 binding, inhibition of proliferation and, ultimately, apoptosis.
Garvy
B A
BA
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Riley
R L
RL
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015851:Interleukin-7 / Q000037:antagonists & inhibitors*; D017493:Leukocyte Common Antigens; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000276:immunology
D000954:Antigens, Surface; D015851:Interleukin-7; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens