Modulation of B-cell proliferative response by a soluble extract of Nippostrongylus brasiliensis

We and others have previously shown that nematodes or nematode products can stimulate or inhibit the generation of lymphocyte responses, suggesting th at nematodes exert diverse effects on the developing immune responses of th eir host. In this study we examined the immunomodulatory effect of a solubl e extract of Nippostrongylus brasiliensis (adult worm homogenate [AWH]) on B-cell responsiveness. We found that the extract inhibited the proliferatio n of B cells to lipopolysaccharide (LPS) stimulation in a dose-dependent ma nner. This effect was specific to B cells, since the extract did not inhibi t 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 in hibitory 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 myr istate 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 prolif eration. We present evidence that, in the absence of accessory cells, the i nhibitory effect of the extract was ablated, This observation shows that th e activity of AT VH is not mediated directly on B cells but is mediated via the production of negative signals from accessory cells (macrophages), whi ch affect a downstream pathway required by all B-cell activators tested. Th ese effects on B-cell and accessory cell function are likely to have a sign ificant effect on the outcome of infections experienced concurrently.