IL-10 INHIBITS LL-7-MEDIATED MURINE PRE-B-CELL GROWTH IN-VITRO

B lymphopoiesis in the bone marrow is mediated by both positive and ne gative regulatory cytokines. In this report, we demonstrate that inter leukin-10 (IL-10) may function to inhibit murine IL-7-dependent pre-B cell growth. Recombinant IL-10 (rmIL-10) inhibited BALB/c bone marrow IL-7 colony-forming unit (CFU) in a concentration-dependent manner, an d growth was restored when IL-10 was neutralized with the monoclonal a nti-IL-10 antibody, SXC-1. Enriched populations of B220(+) bone marrow B lineage cells were also inhibited in their responses to IL-7 by exp osure to rmIL-10, suggesting that pre-B cells were directly susceptibl e to rmIL- 10 inhibition. Heterogeneity in the capacity of IL-7 CFU to be inhibited by IL-10 was evident. Although 60% of IL-7 CFU were inhi bited by rmIL-10 at 5 U/mL, approximately 20% of IL-7 CFU were not inh ibited by rmIL-10 concentrations up to 50 U/mL. Prior incubation of bo ne marrow cells for 24 hours with IL-7 prevented rmIL-10-mediated grow th inhibition, suggesting that prior rIL-7 stimulation of pre-B cells abrogates the inhibitory effects of rmIL-10. These experiments indicat e that IL-10, at these concentrations, may function as a potent negati ve growth regulator for a significant fraction of IL-7-responsive pre- B cells.