title: A factor of inducing IgE from a filarial parasite is an agonist of human CD40.
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.
authors.affiliation: Section of Environmental Parasitology, Department of International Health Development, Division of Public Health, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8519. sitimai@ac.mnb.or.jp
authors.forename: S
authors.initials: S
authors.lastname: Imai
authors.forename: H
authors.initials: H
authors.lastname: Tezuka
authors.forename: Y
authors.initials: Y
authors.lastname: Furuhashi
authors.forename: R
authors.initials: R
authors.lastname: Muto
authors.forename: K
authors.initials: K
authors.lastname: Fujita
mesh_terms: D000818:Animals; D001483:Base Sequence; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D004183:Dirofilaria immitis / Q000502:physiology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D017931:DNA Primers; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007073:Immunoglobulin E