A new approach to comparing anti-CD20 antibodies: importance of the lipid rafts in their lytic efficiency

Mariam Hammadi, Jacques-Olivier Pers, Christian Berthou, Pierre Youinou, Anne Bordron

Centre Hospitalier Universitaire EA2216 and IFR148, Université de Bretagne Occidentale and Université Européenne de Bretagne, BP824, 29609 Brest cedex, France

Abstract: The view that B lymphocytes are pathogenic in diverse pathological settings is supported by the efficacy of B-cell-ablative therapy in lymphoproliferative disorders, autoimmune diseases and graft rejection. Anti-B-cell antibodies (Abs) directed against CD20 have therefore been generated, and of these, rituximab was the first anti-CD20 monoclonal Ab (mAb) to be applied. Rituximab-mediated apoptosis, complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity differ from one disease to another, and, for the same disease, from one patient to another. This knowledge has prompted the development of new anti-CD20 mAbs in the hope of improving B-cell depletion. The inclusion of CD20/anti-CD20 complexes in large lipid rafts (LRs) enhances the results of some, but not all, anti-CD20 mAbs, and it may be possible to include smaller LRs. Lipid contents of membrane may be abnormal in malignant B-cells, and could explain resistance to treatment. The function of these mAbs and the importance of LRs warrant further investigation. A detailed understanding of them will increase results for B-cell depletion in lymphoproliferative diseases.

Keywords: anti-CD20 antibodies, lymphocyte B, lipid rafts, B-cell disorders