Human lymphocytotoxic monoclonal autoantibodies from a highly sensitized renal dialysis patient.
A panel of 5 human monoclonal autolymphocytotoxic antibodies (IRM-3, IRM-4, IRM-7, IRM-8, and IRM-10) of the IgM class was established from a highly sensitized renal dialysis patient (IRM), by the generation of mouse-human heterohybridomas. This panel was screened for reactivity against foreign and autoantigens by ELISA, and for reactivity against different tissue sections and HEp-2 slide preparations by indirect immunofluorescence. Cytotoxicity screening of heterohybridoma supernatants gave broad panel reactivity profiles, being cytotoxic against B cells from patient IRM and also against most B cells tested and less reactive with chronic lymphocytic leukemia B cells; T cells were the least sensitive target. Immunoblotting showed that monoclonal IRM displayed some heterogeneity in their binding profiles, although all of them recognized a cellular structure of 26 kDa. None of the heterohybridoma cell lines exhibited cytoplasmic nor surface staining with an anti-CD5 mAb. Results obtained showed that all the autolymphocytotoxic mAbs generated were also able to react against certain nuclear and cytoplasmic self-structures as well as foreign compounds. Monoclonal antibody IRM-7 and, to a lesser degree, IRM-10 exhibited multispecific properties similar to those observed for polyreactive or natural antibodies.
Robledo
M M
MM
Servicio de Inmunología, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Melero
J
J
Dinca
L
L
Tarragó
D
D
García-Lozano
J R
JR
Núñez-Roldán
A
A
Sánchez
B
B
D000911:Antibodies, Monoclonal / Q000097:blood*; D000961:Antilymphocyte Serum; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006435:Renal Dialysis
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D001323:Autoantibodies