Abstract
Immune responses to parasitic helminth are usually characterized by quite mysterious phenomena: dominance of Th2-like immunity and antigen-nonspecific IgE secretion. We previously purified a factor from Dirofilaria immitis that induces antigen-nonspecific IgE in rats and named it DiAg. In the presence of IL-4, DiAg induces mouse B cells to secrete IgE, which is antigen-nonspecific polyclonal antibody. We investigated the biochemical characteristics of DiAg as a factor of inducing IgE in this study. Recombinant DiAg (rDiAg) with interleukin (IL)-4 induced IgE synthesis in highly purified human normal B cells in vitro cell culture systems. The addition of recombinant human soluble CD40 IgG fusion protein (rsCD40-Ig) inhibited induction of IgE synthesis by rDiAg with IL-4. Monocyte cells were stimulated with rDiAg and recombinant human soluble CD40L (rsCD40L); IL-12 and TNF-alpha were induced. The addition of rsCD40-Ig to THP-1 cells activated with rDiAg and rsCD40L inhibited the production of IL-12. rDiAg bound to the monocyte cell membrane fraction and recombinant human soluble CD40; this binding of rDiAg was competitively inhibited by addition of rsCD40L. Moreover, in CD40-deficient mice, IgE production and MLN-B cell proliferation by rDiAg were completely absent. Based on these results, we concluded that DiAg is an agonist of CD40.
Highlights
Parasitic helminth infections are characterized by mast cell hyperplasia, eosinophilia [1], and markedly elevated levels of circulating antigen nonspecific IgE [2], which responses were concerned to helminth protection [3, 4]
To assess the role of CD40 with its ligand (CD40L) in the induction of IgE synthesis by Recombinant DiAg (rDiAg) in normal B cells, we examined the effect of blocking CD40L-CD40 interactions
When dendritic cells (DC) were activated by co-culture with CD40L transfectants, TNF-␣ were not significantly affected by the addition of IL-10, but IL-12 levels were markedly decreased [32]
Summary
We previously purified a factor from Dirofilaria immitis that induces antigen-nonspecific IgE in rats and named it DiAg. In the presence of IL-4, DiAg induces mouse B cells to secrete IgE, which is antigennonspecific polyclonal antibody. A number of critical questions about the mechanisms of polyclonal IgE synthesis remain to be resolved It is not clear which molecules play an essential role in DiAg-induced activation of B cells. RDiAg has been previously shown to induce IgE secretion of splenic B cells from naive mice with IL-4 in vitro culture system in the absence of T cells.1 It suggests that the engagement of antigen-specific T cell to B cells is not involved in induction of IgE by rDiAg. DiAg might induce the IgE class switching via the CD40 molecule with the IL-4. We report here that rDiAg have various biological activity to the human cell lines and B cell population
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