Independent trafficking of Ig-alpha/Ig-beta and mu-heavy chain is facilitated by dissociation of the B cell antigen receptor complex.
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.
Kim
Jin-Hyang
JH
Department of Pathology and the Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Cramer
Lorraine
L
Mueller
Heather
H
Wilson
Bridget
B
Vilen
Barbara J
BJ
D000818:Animals; D017951:Antigen Presentation; D001693:Biological Transport, Active; D002460:Cell Line; D022163:Clathrin-Coated Vesicles / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis; D005677:G(M1) Ganglioside / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007137:Immunoglobulin alpha-Chains / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000378:metabolism; D007700:Kinetics; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
D007143:Immunoglobulin Heavy Chains; D007137:Immunoglobulin alpha-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D005677:G(M1) Ganglioside