title: The human natural killer cytotoxic cell line NK-92, once armed with a murine CD16 receptor, represents a convenient cellular tool for the screening of mouse mAbs according to their ADCC potential.
abstract: To take advantage of the large number of well-characterized mouse immunoglobulins (IgGs) for the study of antibody-dependent cell-mediated cytotoxicity (ADCC) in human cells, we armed human cytotoxic lymphocytes with a mouse receptor for the Fc portion of IgG antibodies. The human ΝΚ-92 natural killer cell line was transduced with a mouse receptor gene (mCD16), which was stably expressed on the cell surface (referred to as NK-92 (mCD16) ). When tested against a B-lymphoblastoid cell line (BLCL) coated with mouse anti-CD20 IgG1, IgG2a or IgG2b monoclonal antibodies (mAbs), the newly expressed mouse Fc receptor enabled the NK-92 (mCD16) cells to kill the BLCL by ADCC. Next, using the NK-92 (mCD16) we compared mouse mAbs directed at B lineage specific CD antigens for their ability to induce ADCC against human Epstein-Barr virus- infected B lymphoblastoid (for anti-CD19, -CD20 and -CD21) or against myeloma (for anti-CD38 and -CD138) target cells. Our results demonstrated that the "NK-92 (mCD16) assay" allows convenient and sensitive discrimination of mouse mAbs for their ability to mediate ADCC in a human cellular system. In addition, our results provide examples of dissociation between opsonization and target cell killing through ADCC. These "murinized" human effector cells thus represent a convenient cellular tool for the study of ADCC.
authors.affiliation: INSERM U892, Nantes, France. beatrice.clemenceau@inserm.fr
authors.forename: Béatrice
authors.initials: B
authors.lastname: Clémenceau
authors.forename: Régine
authors.initials: R
authors.lastname: Vivien
authors.forename: Catherine
authors.initials: C
authors.lastname: Pellat
authors.forename: Michael
authors.initials: M
authors.lastname: Foss
authors.forename: Gilles
authors.initials: G
authors.lastname: Thibault
authors.forename: Henri
authors.initials: H
authors.lastname: Vié
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002461:Cell Line, Transformed; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009101:Multiple Myeloma / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG
keywords: ADCC; CD16; NK; human; lymphocyte; mouse; transfection; xenogenic