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.
Department of Pathology and the Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Jin-Hyang
JH
Kim
Lorraine
L
Cramer
Heather
H
Mueller
Bridget
B
Wilson
Barbara J
BJ
Vilen
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