Dynamic interplay between the neutral glycosphingolipid CD77/Gb3 and the therapeutic antibody target CD20 within the lipid bilayer of model B lymphoma cells (Journal article)

Jarvis, R. M./ Chamba, A./ Holder, M. J./ Challa, A./ Smith, D. C./ Hodgkin, M. N./ Lord, J. M./ Gordon, J.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
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
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/22316
ISSN: 0006-291X
Link: http://www.ncbi.nlm.nih.gov/pubmed/17336267
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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