We and others have previously shown that nematodes or nematode products can stimulate or inhibit the generation of lymphocyte responses, suggesting that nematodes exert diverse effects on the developing immune responses of their host. In this study we examined the immunomodulatory effect of a soluble extract of Nippostrongylus brasiliensis (adult worm homogenate [AWH]) on B-cell responsiveness. We found that the extract inhibited the proliferation of B cells to lipopolysaccharide (LPS) stimulation in a dose-dependent manner. This effect was specific to B cells, since the extract did not inhibit T-cell proliferation to concanavalin A or anti-CD3 stimulation. The data presented here confirm that the extract is not toxic to B cells. We present evidence that the active factor is proteinaceous in nature and that the inhibitory activity is restricted to the adult stage of Nb. The extract does not appear to interfere with early activation events since it can be added up to 48 h after LPS stimulation, and it inhibited responses to phorbol myristate acetate and ionomycin. Furthermore, the proliferation of B cells to other activators was also inhibited by AWH. This observation shows that the inhibitory activity of AWH is not restricted to LPS-mediated B-cell proliferation. We present evidence that, in the absence of accessory cells, the inhibitory effect of the extract was ablated. This observation shows that the activity of AWH is not mediated directly on B cells but is mediated via the production of negative signals from accessory cells (macrophages), which affect a downstream pathway required by all B-cell activators tested. These effects on B-cell and accessory cell function are likely to have a significant effect on the outcome of infections experienced concurrently.To ensure survival and continuation of their life cycle, nematodes have evolved a unique relationship with their hosts. Part of this accommodation is the ability to modulate host immune responsiveness (25). Modulation of lymphocyte function has been widely reported among nematodes (2,3,19,21,22,28) and other parasites (6,15,27,36). For example, we have previously shown a dramatic potentiation of antibody responses to third party antigens by treatment with a body fluid extract of Ascaris suum (19). This observation is significant in that it suggests that the modulatory effect of nematodes on immune responses is far-reaching and may have profound effects on developing immune responses to unrelated antigenic challenge. We have also reported the presence of a B cell mitogen in the body fluid of A. suum, which stimulated G 0 B cells to enter the cell cycle (20). This activity of the Ascaris factor was dependent on viable accessory cells.The effect of helminth products on the developing immune response is likely to be complex. For example, in contrast to the immunostimulatory activity of the body fluid of Ascaris reported above, Ferreira and coworkers (13) and Soares and coworkers (39, 40) have reported immunomodulatory factors in secretions of A. suum, which a...