The Journal of Immunology, Vol 156, Issue 7 2376-2383, Copyright © 1996 by American Association of Immunologists

ARTICLES

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

LJ Fauteux and DG Osmond
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

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.

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