Here, we report that activin A has a dual role in regulating Ig production of murine B cells. Activated B cells secrete activin activity by increasing activin A and decreasing follistatin expression. B cells also express type I and type II activin receptors, suggesting that they are targets of activin. Pretreatment of naïve B cells with activin A and subsequent activation by LPS resulted in increased cell growth and IgG production. In contrast, no significant effect was observed when activin A was added to naïve B cells simultaneously with LPS, indicating that activin A acts on resting but not activated B cells. In addition, activin A did not induce B cells to produce IgE, even when added prior to activation; however, in vivo antigen-specific IgE production was reduced significantly by neutralization of circulating activin A. These findings indicate that activin A plays an important role in Th2-mediated immune responses by enhancing antibody production through two distinct modes: acts directly on resting B cells to elicit full functions of activated B cells and acts indirectly on activated B cells through modulation of other immune cells.