Dynamic interplay between the neutral glycosphingolipid CD77/Gb3 and the therapeutic antibody target CD20 within the lipid bilayer of model B lymphoma cells.
The centroblast-specific differentiation marker CD77 (Gb(3)), is the receptor for Shiga-like toxin (SLT). The dynamic relationship between Gb(3)/CD77 and key B-cell membrane proteins was studied in Burkitt's lymphoma cells with a focus on CD20. Engagement of Gb(3)/CD77 with SLT-B reduced the amount of CD20 and CXCR4 available, but levels of BCR, MHC Class II, CD21, CD27 and CD54 remained unchanged. Cholesterol depletion promoted a decrease in the number of sites accessed by CD20, CXCR4 and Gb(3)/CD77 antibodies. Constitutive localisation of Gb(3)/CD77 to lipid rafts was unperturbed by either SLT-B binding or cholesterol depletion, whereas the opposite was true for CD20. The effects were specific to SLT-B, highlighted by the inability of cholera toxin B-subunit to alter CD20 availability. Thus, the binding of Gb(3)/CD77 by its cognate ligand transmits information within the lipid bilayer of model lymphoma cells to impact the behaviour of selective proteins, most notably CD20, via a mechanism influenced by the level of cholesterol within the membrane.
Jarvis
Rosemary M
RM
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
Chamba
Anita
A
Holder
Michelle J
MJ
Challa
Anita
A
Smith
Daniel C
DC
Hodgkin
Matthew N
MN
Lord
J Michael
JM
Gordon
John
J
D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002772:Cholera Toxin / Q000494:pharmacology; D006801:Humans; D008051:Lipid Bilayers; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D022603:Shiga Toxins / Q000494:pharmacology; D014281:Trihexosylceramides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
D000906:Antibodies; D018951:Antigens, CD20; D015415:Biomarkers; D008051:Lipid Bilayers; D019253:Proto-Oncogene Proteins c-bcl-2; D022603:Shiga Toxins; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D002772:Cholera Toxin