IL-1 as a systemic modifier of B lymphopoiesis. Recombinant IL-1 alpha binds to stromal cells and sinusoid endothelium in bone marrow and perturbs 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-1 alpha 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 super(+); B220 super(+) mu super(-)), 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-1 alpha produced a proliferative stimulation of pro-B cells and pre-B cells at optimal doses, whereas other doses were suppressive. Infusion of rIL-1 alpha from s.c. osmotic pumps depressed B lymphopoiesis at high dose rates, but stimulated precursor B cell proliferation at lower dose rates. Intravenous super(125)I-labeled rIL-1 alpha bound strongly to a subset of stromal reticular cells and sinusoidal endothelium in BM, as detected by light and electron microscope radioautography. Computer-aided analysis located rIL-1 alpha -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.