Noni juice as a folk medicine has been used for over two thousand years. Recently, some active ingredients of Noni juice have been successfully isolated and intensively studied. Because dendritic cells (DCs) are central regulators both in priming innate and adaptive immune responses and in maintaining self tolerance, in the current study we treated DCs with fermented Noni Exudate (fNE) in order to explore their function in regulating other immune cells. It was shown that fNE-treated DCs stimulate proliferation of splenocytes, among which, B cells are the major responsive cell group. The proliferative response of B cells to fNE-treated DCs is cell contact-dependent, CD40L-independent; and the adhesion feature of DCs was enhanced to form large DC-B conjugation cluster. Moreover, it was demonstrated that fNE-treated DCs promote B cell differentiation and Ig class switching. These results lay a foundation for the further exploration of fNE as a biological response modifier in the immune system.