Early stages of B cell development occur in the bone marrow, resulting in formation of immature B cells. From there these immature cells migrate to the spleen where they differentiate to mature cells. This final maturation step is crucial for the B cells to become responsive to antigens and to participate in the immune response. Recently, invariant chain (Ii), a major histocompatibility complex class II chaperone, as well as the transcription factors c-Rel and p65/RelA, were found to play a role in the final antigen-independent differentiation stage of B cells in the spleen. In this study, we investigated a possible link between Ii-dependent B cell maturation and the NF-kappaB pathway. Our studies indicate that Ii-induced B cell maturation involves activation of transcription mediated by the NF-kappaB p65/RelA homodimer and requires the B cell-enriched coactivator TBP-associated factor (II)105.