IL-1 as systemic modifier of B lymphopoiesis. Recombinant IL-1 alpha binds to stromal cells and sinusoid endothelium in bone marrow and precursor B cell dynamics.
B lymphopoiesis in mouse bone marrow (BM) can be stimulated by circulating products derived from activated macrophages in the spleen. To examine whether IL-1 could mediate this effect, we have administered murine rIL-1alpha in a range of doses, determining its effect on precursor B cells and its capacity to bind to stromal cells in BM. Immunofluorescence labeling of terminal deoxynucleotidyl transferase (TdT), B220 glycoprotein, and mu-chains has been used to quantitate pro-B cells lacking mu (TdT+; 13220+mu-), pre-B cells expressing cytoplasmic mu, and B lymphocytes bearing surface mu. Proliferative activity was measured by mitotic arrest. Single i.p. injections of rIL-1alpha produced a proliferative stimulation of pro-B cells and pre-B cells at optimal doses, whereas other doses were suppressive. Infusion of rIL-1alpha from s.c. osmotic pumps depressed B lymphopoiesis at high dose rates, but stimulated precursor B cell proliferation at lower dose rates. Intravenous 125I-labeled rIL-1alpha bound strongly to a subset of stromal reticular cells and sinusoidal endothelium in BM, as detected by light and electron microscope radio-autography. Computer-aided analysis located rIL-1alpha-binding stromal cells mainly in the outer zones of BM, sites of proliferating precursor B cells, rather than the more central zone. The results demonstrate that IL-1 can act systemically at various dose levels as either a positive or negative modifier of B lymphopoiesis in BM, probably acting indirectly via stromal reticular cells and endothelial cells. Thus, inflammatory processes associated with macrophage activation and IL-1 secretion may have pronounced effects on B cell genesis in BM.
Fauteux
L J
LJ
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Osmond
D G
DG
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D001665:Binding Sites; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism*; D001854:Bone Marrow Cells; D004306:Dose-Response Relationship, Immunologic; D004727:Endothelium / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008854:Microscopy, Electron; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins