Holder Michelle J, Chamba Anita, Hardie Debbie L, Deans Julie P, Gordon John
MRC Centre for Immune Regulation, The Medical School, The University of Birmingham, Vincent Drive, B15 2TT, UK.
Leuk Res. 2004 Nov;28(11):1197-202. doi: 10.1016/j.leukres.2004.02.008.
Here we report that B cell receptor (BCR) engagement rapidly improves the capacity of CD20 to be accessed by cognate antibody at model Burkitt's lymphoma cell surfaces. None of eight other surface molecules demonstrated such BCR-dependent enhancement of ligand binding while the quantity of accessible CD20 remained unchanged on either CD19 or CD40 engagement. Neither the actin-depolymerizing agent cytochalasin D nor inhibitors targeting signalling pathways associated with the BCR attenuated the CD20 increase that could be uncoupled from BCR endocytosis. Instead, a role for lipid rafts was indicated both from the inhibitory actions of cholesterol-sequestering methyl-beta-cyclodextrin and direct analysis of CD20 redistribution using sucrose density gradients and confocal microscopy. Whether such observations could find application in CD20-directed therapies where success can be compromised by otherwise low-level expression of target antigen is discussed.
