This study tested the hypothesis that IL-27 and IL-23, two heterodimeric cytokines involved in physiological immune responses and immunological disorders, may function on human PC and plasmablasts. It was reported that IL-27 acts on human mature B cells, but the role of IL-27 and IL-23 in human PC remains to be established. Thus, we have asked whether these cytokines may modulate human PC functions using human PPC generated in vitro, PC isolated from tonsils, and BM. Here, we show for the first time that PC and PPC express complete IL-27R and that IL-27 exerts chemotactic properties on these cells and modulates different chemokines/chemokine receptors and secretion of IgM and IgG. Furthermore, we demonstrated that PC and PPC express both chains of IL-23R and IL-23 and exerted similar activity to IL-27 in terms of Ig production, while not inducing PC chemotaxis. These results may provide novel insight into the role of IL-27 and IL-23 in human B cell immune responses.