Dynamic interplay between the neutral glycosphingolipid CD77/Gb3 and the therapeutic antibody target CD20 within the lipid bilayer of model B lymphoma cells
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Authors
Jarvis, R. M.
Chamba, A.
Holder, M. J.
Challa, A.
Smith, D. C.
Hodgkin, M. N.
Lord, J. M.
Gordon, J.
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peer-reviewed
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Biochem Biophys Res Commun
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Description
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.
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Keywords
Antibodies/*immunology/therapeutic use, Antigens, CD20/*immunology/metabolism, Apoptosis/drug effects, Biological Markers, Burkitt Lymphoma/*immunology/*metabolism/pathology, Cell Line, Tumor, Cholera Toxin/pharmacology, Humans, Lipid Bilayers, Membrane Microdomains/drug effects/metabolism, *Models, Biological, Proto-Oncogene Proteins c-bcl-2/genetics/metabolism, Shiga Toxins/pharmacology, Trihexosylceramides/chemistry/*immunology/*metabolism
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http://www.ncbi.nlm.nih.gov/pubmed/17336267
http://ac.els-cdn.com/S0006291X07003300/1-s2.0-S0006291X07003300-main.pdf?_tid=a9e49f6e6e0b9f428643e986e75a269b&acdnat=1332919373_2c99d66223a99fe1a8138f7896b5c150
http://ac.els-cdn.com/S0006291X07003300/1-s2.0-S0006291X07003300-main.pdf?_tid=a9e49f6e6e0b9f428643e986e75a269b&acdnat=1332919373_2c99d66223a99fe1a8138f7896b5c150
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en
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής