Modulation of B-Cell Proliferative Response by a Soluble Extract of Nippostrongylus brasiliensis

Abstract

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.

Requirements for the development of IL‐4‐producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo

“…Alternatively, if N. brasiliensis alone stimulated DO11.10 Th2-cell differentiation, then it would suggest that either the OVA-specific TCR cross-reacted with antigens expressed by the N. brasiliensis parasite or that this parasite released factors that could nonspecifically activate T cells. There is some precedence for nonspecific effects of N. brasiliensis on adaptive immunity, as this parasite has been reported to modulate T-and B-cell activation (12)(13)(14). The results that we obtained in these experiments, however, showed that pronounced levels of IL-4 gene and protein expression were detected in the draining lymph node only when the combination of OVA and N. brasiliensis were administered as the inoculum (7).…”