Dendritic cell development and survival require distinct NF-kappaB subunits

Despite the established role of dendritic cells (DCs) in regulating T lymphocyte activation, intracellular mechanisms responsible for controlling DC function are largely undefined. Here, we have studied DCs from mice deficient in the p50, RelA, and cRel subunits of the immunomodulatory NF-kappaB transcription factor. Although DC development and function was normal in mice lacking individual NF-kappaB subunits, development of doubly deficient p50(-/-)RelA(-/-) DCs was significantly impaired. In contrast, DCs from p50(-/-)cRel(-/-) mice developed normally, but CD40L- and TRANCE-induced survival and IL-12 production was abolished. Surprisingly, no significant impairment in MHC and costimulatory molecule expression was seen, despite significantly reduced kappaB site binding activity. These results therefore indicate essential, subunit-specific functions for NF-kappaB proteins in regulating DC development, survival, and cytokine production.