TY - JOUR
T1 - A Factor of Inducing IgE from a Filarial Parasite Is an Agonist of Human CD40
AU - Imai, Shinjiro
AU - Tezuka, Hiroyuki
AU - Furuhashi, Yuko
AU - Muto, Riho
AU - Fujita, Koichiro
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2001/12/7
Y1 - 2001/12/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035824584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035824584&partnerID=8YFLogxK
U2 - 10.1074/jbc.M104581200
DO - 10.1074/jbc.M104581200
M3 - Article
C2 - 11591702
AN - SCOPUS:0035824584
VL - 276
SP - 46118
EP - 46124
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 49
ER -