INFLUENCE OF IL-10 ON MURINE CFU-PRE-B FORMATION

We have examined the ability of interleukin-10 (IL-10) to influence murine B cell development in vitro and in vivo. In vitro treatment of young adult mouse bone marrow cells with 0.5 to 10 ng/ml human IL-10 (hIL-10) produced a significant enhancement of IL-7-mediated colony-forming unit-pre-B (CFU-pre-B) formation, while IL-10 concentrations >10 ng/ml had no net effect. IL-10 by itself was unable to stimulate pre-B cell colony formation, even at optimal concentrations. The increase in CFU-pre-B produced by IL-10 was specifically blocked by anti-hIL-1O antibody, but not by anti-stem cell factor (SCF) antibody, and was observed with both unfractionated and purified B220(+) surface immunoglobulin (sIg(-)) bone marrow cells. CFU-pre-B from the IL-10 treatment group contained a higher percentage of CD43(+)B220(+) blast-like cells than colonies exposed to IL-7 only. In vivo administration of 0.1 mu g hIL-10 per day to mice treated with a single sublethal dose of cyclophosphamide (CY) resulted in a dramatic and accelerated recovery of CFU-pre-B numbers as compared to vehicle-administered mice. This enhancement was seen as early as day 11 post-CY, and the number of CFU-pre-B was comparable to normal age-matched control mice by day 16. In contrast, the number of CFU-pre-B in vehicle-treated mice remained significantly lower than age-matched and IL-1O-treated animals as long as day 22 post-CY. No differences in the number of pre-B and mature B cells in bone marrow or in the number of mature B cells in peripheral lymphoid organs were detected in IL-1O-treated mice. Myeloid cell recovery, assessed by the CFU-granulocyte/macrophage (CFU-GM) assay and the number of marrow Mac-1(+) cells, was unaffected by IL-10 treatment of CY-dosed animals. These results indicate that IL-10 enhanced IL-7-stimulated murine pre-B cell colony formation and imply a role for IL-10 in normal B lymphopoiesis.