The transcription factors NF-κB1 and c-Rel serve distinct roles in conventional and plasmacytoid dendritic cells activated by engaging TLR-9. This diagram depicts the distinct roles for c-Rel and NF-κB1 in cDCs and pDCs prior to encountering microbial signals (steady state) and in response to CpG-ODN–mediated activation via TLR-9/MyD88. Survival-dependent and -independent mechanisms regulated by these transcription factors control splenic cDC and pDC numbers. For CpG-activated cDCs, c-Rel is necessary for IL-12p70 expression, whereas for CpG-stimulated pDCs, these transcription factors in addition to regulating IL-12p70 production, control IL-6 synthesis, morphologic transformation during differentiation, the expression of key activation markers, and survival.