Placental protein 14 (PP14) is a glycoprotein of the lipocalin family that acts as a negative regulator in T cell receptor-mediated activation. In this study, we investigated PP14s potential role in regulating B cell activation. While PP14-inhibited B cell proliferation, IgM secretion and the surface expression of MHC class II, the expression of other surface molecules, such as CD69 and CD86, were unaffected. These observed effects were independent of the anti-IgM concentration used for stimulation, regardless of the presence of either T cells or IL-4, and persisted when B cells were stimulated by stimuli, which circumvent early events during B cell Ag receptor (BCR) activation, namely, protein kinase C activators in combination with Ca(2+) ionophore. Interestingly, we demonstrated that PP14s inhibitory characteristics are reminiscence of that achieved by independent ligation of CD19 using anti-CD19 mAb. Together with our previously reported effects on T cells, these findings identify PP14 as a soluble regulatory factor capable of interacting with both T and B cells in a carbohydrate-dependent manner and as a result it can affect both cellular and humoral immune responses.