Abstract: Dendritic cells (DCs), which represent a key type of antigen‐presenting cell (APC), are important for the development of innate and adaptive immunity. DCs are involved in T cell activation in at least two main ways: priming via direct processing/presentation of soluble antigen taken up from the microenvironment (conventional priming), and processing/presentation of antigen released from other cells (cross‐priming). relB, a component of the NF‐κB complex of transcription factors, is a critical regulator of the differentiation of DCs. In mice, lack of relB impairs DCs derived from bone marrow both in number and function. Here relB (−/−) bone marrow chimera mice is used to study the APC function of residual DCs in presentation of soluble antigen and cross‐priming. It is found that the DCs in these mice are profoundly deficient in their ability to both prime and cross‐prime T cell responses. It was concluded that the relB gene is involved in regulating the APC function of DCs in vivo.