A Factor of Inducing IgE from a Filarial Parasite Is an Agonist of Human CD40

Shinjiro Imai, Hiroyuki Tezuka, Yuko Furuhashi, Riho Muto, Koichiro Fujita

Research output: Contribution to journalArticle

20 Citations (Scopus)

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-α 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.

Original languageEnglish
Pages (from-to)46118-46124
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number49
DOIs
Publication statusPublished - 07-12-2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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