SHIP^−/− BMmφs produce high levels of IFN-β after a first dose of dsRNA or LPS and markedly elevated IFN-β levels in response to a second dose. (A) SHIP^+/+ (□) and SHIP^−/− (■) BMmφs were primed with dsRNA or LPS and 24 hours cell supernatants assessed for IFN-β by ELISA. Results are the mean plus or minus SEM of 3 independent experiments assayed in duplicate. *P < .05 compared with SHIP^+/+ cells. (B) SHIP^+/+ (□) and SHIP^−/− (■) BMmφs were untreated (0) or primed with 30 nM CpG, 5 μg/mL dsRNA, or 10 ng/mL LPS for 24 hours and then stimulated with either 5 μg/mL dsRNA (left panel) or 10 ng/mL LPS (right panel). Cell supernatants were harvested 24 hours later and assessed for IFN-β by ELISA. Unstimulated cells did not produce detectable IFN-β levels. Results are the mean plus or minus SEM of 3 or 4 independent experiments assayed in duplicate. *P < .001 compared with untolerized cells. **P < .02 compared with untolerized cells and compared with SHIP^+/+ cells. ***P < .01 compared with untolerized cells but not significantly different from SHIP^+/+ cells. NS indicates not significant.