The BCR relays extracellular signals and internalizes Ag for processing and presentation. We have previously demonstrated that ligation of the BCR destabilizes Ig-alpha/Ig-beta (Ig-alphabeta) from mu-H chain (mum). In this study we report that receptor destabilization represents a physical separation of mum from Ig-alphabeta. Sucrose gradient fractionation localized Ig-alphabeta to G(M1)-containing lipid microdomains in the absence of mum. Confocal and electron microscopy studies revealed the colocalization of unsheathed mum with clathrin-coated vesicles. Furthermore, mum failed to associate with clathrin-coated vesicles when receptor destabilization was inhibited, suggesting that unsheathing of mum is required for clathrin-mediated endocytosis. In summary, we found that Ag stimulation physically separates Ig-alphabeta from mum, facilitating concomitant signal transduction and Ag delivery to the endocytic compartment.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895480PMC
http://dx.doi.org/10.4049/jimmunol.175.1.147DOI Listing

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