IL-10 inhibits IL-7-mediated murine pre-B cell growth in vitro

B lymphopoiesis in the bone marrow is mediated by both positive and negative regulatory cytokines. In this report, we demonstrate that interleukin-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, and growth was restored when IL-10 was neutralized with the monoclonal anti-IL-10 antibody, SXC-1. Enriched populations of B220+ bone marrow B lineage cells were also inhibited in their responses to IL-7 by exposure to rmIL-10, suggesting that pre-B cells were directly susceptible 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 inhibited by rmIL-10 at 5 U/mL, approximately 20% of IL-7 CFU were not inhibited by rmIL-10 concentrations up to 50 U/mL. Prior incubation of bone marrow cells for 24 hours with IL-7 prevented rmIL-10-mediated growth inhibition, suggesting that prior rIL-7 stimulation of pre-B cells abrogates the inhibitory effects of rmIL-10. These experiments indicate that IL-10, at these concentrations, may function as a potent negative growth regulator for a significant fraction of IL-7-responsive pre-B cells.