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.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy