TY - JOUR
T1 - B cell activation regulates exosomal HLA production
AU - Arita, Shuji
AU - Baba, Eishi
AU - Shibata, Yoshihiro
AU - Niiro, Hiroaki
AU - Shimoda, Shinji
AU - Isobe, Taichi
AU - Kusaba, Hitoshi
AU - Nakano, Shuji
AU - Harada, Mine
PY - 2008/5
Y1 - 2008/5
N2 - Exosomes are nanovesicles produced constitutively and inducibly by several types of cells. They are generated as intraluminal vesicles of multivesicular bodies and express MHC and several endosomal/lysosomal proteins. In spite of their potential role in cellular immunity, the regulatory mechanisms of exosome production are largely unknown. in this study, we have established a novel ELISA system to quantify exosomal HLA using a combination of anti-HLA class I and anti-HLA-DR mAb. We found that exosomal HLA production of B cells was enhanced by contactwith CD4+T cells. Neutralizing anti-CD154 (CD40L) mAb inhibited this effect, and a soluble CD40I. significantly increased production of exosomal HLA in B cells. In addition, B cell stimulation via BCR and TLR9 enhanced their production while IL-4 stimulation alone failed to do so. Strikingly, an inhibitor of the classical NF-κB pathway drastically inhibited exosomal HLA production in stimulated B cells, indicating that the classical NF-κB pathway is criticol for exosomal HLA production in B cells. Together, these findings suggest a pivotal role of B cell activation in exosomal HLA production in vivo.
AB - Exosomes are nanovesicles produced constitutively and inducibly by several types of cells. They are generated as intraluminal vesicles of multivesicular bodies and express MHC and several endosomal/lysosomal proteins. In spite of their potential role in cellular immunity, the regulatory mechanisms of exosome production are largely unknown. in this study, we have established a novel ELISA system to quantify exosomal HLA using a combination of anti-HLA class I and anti-HLA-DR mAb. We found that exosomal HLA production of B cells was enhanced by contactwith CD4+T cells. Neutralizing anti-CD154 (CD40L) mAb inhibited this effect, and a soluble CD40I. significantly increased production of exosomal HLA in B cells. In addition, B cell stimulation via BCR and TLR9 enhanced their production while IL-4 stimulation alone failed to do so. Strikingly, an inhibitor of the classical NF-κB pathway drastically inhibited exosomal HLA production in stimulated B cells, indicating that the classical NF-κB pathway is criticol for exosomal HLA production in B cells. Together, these findings suggest a pivotal role of B cell activation in exosomal HLA production in vivo.
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U2 - 10.1002/eji.200737694
DO - 10.1002/eji.200737694
M3 - Article
C2 - 18425730
AN - SCOPUS:47049109897
VL - 38
SP - 1423
EP - 1434
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 5
ER -