We have shown previously that in vitro-generated human dendritic cells have an effect on the response of B cells at various stages of their differentiation. In a culture system described for the in vitro induction of plasma-cell differentiation, it was reported that naïve B cells have a poor propensity to differentiate into plasma cells. In such a culture system, 12% of naïve B cells differentiated into plasma cells in the presence of IL-2 and IL-10, despite the interruption of CD40 signalling which is necessary for plasma-cell differentiation. However, as reported herein, naïve B cells differentiated fully into plasma cells in response to dendritic cells. Addition of dendritic cells enhanced this differentiation strikingly by recruiting 57% of B cells as plasma cells producing IgM, but also IgG and IgA. In this model, dendritic cells act in synergy with IL-2 at an early stage of CD40-dependent B-cell differentiation, while IL-2 and IL-10 act together, at a later stage, in the generation of plasma cells in a CD40-independent manner. Thus, in addition to the key role played by dendritic cells in the initiation of T-cell responses, our results suggest that dendritic cells regulate humoral responses.