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

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

Floridoside Extracted from the Red Alga Mastocarpus stellatus Is a Potent Activator of the Classical Complement Pathway

Many biological properties of algae have been found to have useful applications in human health, particularly in the fields of oncology and immunology. Floridoside, extracted from the red alga Mastocarpus stellatus, has a structure similar to the xenoantigen Gal alpha 1–3 Gal. This xenoantigen has been described to induce a high immune response in human xenografts and is mediated by natural anti-gal antibodies that activate the classical complement pathway. Based on this property, we analyzed the potential activities of floridoside on the immune system. We demonstrated that floridoside activates a complement cascade via the classical complement pathway, through the recruitment and activation of natural IgM. This algal molecule could represent an important step in the development of a potent new anticomplementary agent for use in therapeutic complement depletion

Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling

Abstract Oligosaccharides are implicated in the development of the immune response notably in complement activation. Anti-tumoural immunotherapy by monoclonal antibodies (mAbs) offers some advantages to chemotherapy including cell targeting but some of them are inefficient to generate cytotoxicity dependent complement (CDC) known to be important in the antibody\u2019s efficacy. The aim of this study is to give a CDC activity of mAb by linkage of a complement activating oligosaccharide to this antibody via a hetero-bifunctional linker allowing control of the conjugation reaction. We worked on non Hodgkin Burkitt\u2019s lymphoma as cancer source, Fab fragments of rituximab devoid of complement activity as mAb and the trisaccharide Gal\u3b1(1\u21923)Gal\u3b2(1\u21924)GlcNAc as immunogenic glycan. The bioconjugate Fab-Gal was characterized by biochemical methods and we demonstrated that the \u3b1-Gal epitope was recognized by seric immunoglobulins. After checking the recognition capacity of the Fab- Gal conjugate for the CD20 epitope, in vitro assays were performed to evaluate the activation of the complement cascade by the Fab-Gal conjugate. The effect of this bioconjugate was confirmed by the evaluation of the proliferation response of Burkitt\u2019s cell line. The relative facility realization of this strategy represents new approaches to increase activities of mAbs

Effets pathogènes des auto-anticorps anti-cellules endothéliales à l'encontre de leurs cellules cibles

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Comprendre la physiopathologie des lymphocytes B au cours de la leucmie lymphoïde chronique : role des lymphocytes B régulateurs.

International audienc

Identification and role of regulatory B cells in chronic lymphocytic leukemia.

International audienc

An ASP application in integrative biology: identification of functional gene units

International audienceIntegrating heterogeneous knowledge is necessary to eluci- date the regulations in biological systems. In particular, such an inte- gration is widely used to identify functional units, that are sets of genes that can be triggered by the same external stimuli, as biological stresses, and that are linked to similar responses of the system. Although several models and algorithms shown great success for detecting functional units on well-known biological species, they fail in identifying them when ap- plied to more exotic species, such as extremophiles, that are by nature unrefined. Indeed, approved methods on unrefined models suffer from an explosion in the number of solutions for functional units, that are merely combinatorial variations of the same set of genes. This paper overcomes this crucial limitation by introducing the concept of "genome segments". As a natural extension of recent studies, we rely on the declarative model- ing power of answer set programming (ASP) to encode the identification of shortest genome segments (SGS). This study shows, via experimental evidences, that SGS is a new model of functional units with a predic- tive power that is comparable to existing methods. We also demonstrate that, contrary to existing methods, SGS are stable in (i) computational time and (ii) ability to predict functional units when one deteriorates the biological knowledge, which simulates cases that occur for exotic species

Global changes in DNA hydroxymethylation and defective TET2 expression predict poor prognosis in chronic lymphocytic leukemia.

International audienc

Global changes in DNA hydroxymethylation and defective TET2 expression predict poor prognosis in chronic lymphocytic leukemia.

International audienc

Les lymphocytes B de leucémie lymphoïde chronique, des lymphocytes B régulateurs qui s’ignorent ?

International audienc