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Anti-CD20 therapeutic antibody rituximab modifies the functional organization of rafts/microdomains of B lymphoma cells

Kulangara, Karina
Klages, Natacha
van Echten-Deckert, Gerhild
Published in Cancer Research. 2003, vol. 63, no. 2, p. 534-540
Abstract Incubation of Burkitt lymphoma-derived Raji cells at physiological temperature with submicromolar concentrations of humanized anti-CD20 antibody rituximab (RTX) redistributes CD20 to liquid-ordered, plasma membrane rafts. This accumulation of the CD20 tetraspan protein in rafts does not change the existing lipid and phosphoprotein composition but makes sphingolipids and the Src regulator Cbp/PAG (Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched microdomain) transmembrane phosphoprotein more resistant to n-octyl-beta-pyranoside, a detergent that dissociates sphingolipid clusters. On the contrary, sphingolipids and Cbp/PAG are not protected by the presence of CD20 against the disruptive effects of methyl-beta-cyclodextrin, a cyclic carbohydrate that removes membrane cholesterol. After accumulation of CD20, the activity of the raft-associated Lyn kinase is down-regulated without apparent alteration of its relationship to substrates. Moreover, in rafts of lymphoblastoid cells that express lower amounts of Cbp/PAG, RTX redistributes CD20 to rafts but does not modulate the raft-associated protein tyrosine kinase activity, suggesting that the presence of Cbp/PAG protein in rafts is necessary for RTX to exert its transmembrane "signaling effects." Lastly, redistribution of CD20 in rafts renders the glycosylphosphatidyl inositol (GPI)-linked CD55 C'-defense protein hypersensitive to glycosylphosphatidyl inositol-specific phospholipases. By redistributing CD20 to rafts, RTX modifies their stability and organization and modulates the associated signaling pathways and C' defense capacity.
Keywords Antibodies, Monoclonal/ pharmacologyAntigens, CD20/ metabolismAntigens, CD55/metabolismAntineoplastic Agents/ pharmacologyCyclodextrins/chemistryGlucosides/chemistryHumansLymphoma, B-Cell/drug therapy/ metabolismMembrane Lipids/metabolismMembrane Microdomains/drug effects/ metabolismMembrane Proteins/metabolismPhospholipase D/metabolismPhosphoproteins/metabolismType C Phospholipases/metabolismbeta-Cyclodextrinssrc-Family Kinases/metabolism
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PMID: 12543813
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