Adhesion and signaling by B cell‐derived exosomes: the role of integrins

ABSTRACT Exosomes are nanometer‐sized vesicles secreted by various cells, with potentially diverse roles in physiology. Although emphasis has been placed on their involvement in immune modulation, their potential for more wide‐ranging biological effects has not been appreciated. A common exosome feature is the expression of adhesion molecules, which include the integrin family. We have for the first time addressed the possible function of B cell‐derived exosome‐integrins by examining adhesive interactions of exosomes (immobilized onto beads) with extracellular matrix (ECM) components and cytokine‐treated fibroblasts. Integrin (β1 and β2) expression was demonstrated by Western blotting and flow cytometry. Binding studies (with blocking antibodies) demonstrated their function in adhesion to collagen‐I, fibronectin, and tumor necrosis factor (TNF)‐α‐activated fibroblasts. Exosome adhesion to TNF‐α‐activated fibroblasts also triggered integrin‐dependent changes in cytosolic calcium, measured by single cell imaging. Thus, B cell‐derived exosomes express functional integrins, which are capable of mediating anchorage to ECM and cell‐surface adhesion molecules, and may be a novel mode of delivering adhesion signals at distances beyond that of direct cell‐cell contact during inflammation.