Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 5, Pages 1423-1434Publisher
WILEY
DOI: 10.1002/eji.200737694
Keywords
B cells; exosomes; HLA; NF-kappa B
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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 contact with CD4(+) T cells. Neutralizing anti-CD154 (CD40L) mAb inhibited this effect, and a soluble CD40L 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-kappa B pathway drastically inhibited exosomal HLA production in stimulated B cells, indicating that the classical NF-kappa B pathway is critical 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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