Production and characterization of human monoclonal lymphocytotoxic autoantibodies from a renal dialysis patient.
We have produced human monoclonal lymphocytotoxic autoantibodies from a renal dialysis patient by the generation of a mouse/human heterohybridoma. The antibodies are of the IgM class and react with the patient's autologous cells, the B-lymphoblastoid cell line producing the antibody, normal T and B lymphocytes, B cells from chronic lymphatic leukemia patients (CLL cells), and the autoantibody-sensitive cell line K562. Screening of the monoclonal antibodies (mAb) against panels of normal T and B cells and CLL cells demonstrated that different reactivity profiles could be generated at different dilutions of the mAb. These profiles were identical to those seen with autoantibodies from different renal patients and this suggests that these profiles do not imply different antibody specificities but differing target cell sensitivity. Reactivity profiles seen in the fluorescence binding assays suggest that the target cell sensitivity is dictated not by antigen density alone but also by antibody/antigen affinity. The results from studies of enzyme treatment of target cells and lectin inhibition of the molecular specificity suggest that the autoantibodies are polyreactive, capable of binding sialic acid-dependent epitopes and other negatively-charged cell surface molecules.
Taylor
C J
CJ
Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, UK.
Ting
A
A
Morris
P J
PJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification*; D001324:Autoantigens / Q000276:immunology; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology / Q000302:isolation & purification*; D007676:Kidney Failure, Chronic / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D006435:Renal Dialysis
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D007075:Immunoglobulin M