Lineage-restricted function of nuclear factor κB-inducing kinase (NIK) in transducing signals via CD40

CD40 signaling in B cells and dendritic cells (DCs) is critical for the development of humoral and cell-mediated immunity, respectively. Nuclear factor kappa B (NF-kappa B)-inducing kinase (NIK) has been implicated as a central transducing kinase in CD40-dependent activation. Here, we show that although NIK is essential for B cell activation, it is dispensable for activation of DCs. Such data provide compelling evidence that different intermediary kinases are used by different cellular lineages to trigger NF-kappa B activation via CD40.