A human fetal monoclonal DNA-binding antibody shares idiotypes with fetal and adult murine monoclonal DNA-binding antibodies.
A human DNA-binding monoclonal antibody was produced by fusing the hepatocytes from a 12-week-old human fetus with the lymphoblastoid cell line GM 4672 using polyethylene glycol. This antibody, designated BEG 2, binds to single-stranded (ss) DNA but also binds to double-stranded (ds) DNA, poly(dT), polyI and poly(ADP-ribose), but not to RNA, cardiolipin or K-30. The binding of BEG 2 to these polynucleotides can be inhibited by incubation with polynucleotides in the fluid phase. A rabbit polyclonal anti-idiotype was raised, and using this reagent it was shown that the BEG 2 idiotype is present in normal human serum (7%), systemic lupus erythematosus (SLE) sera (8%) and rheumatoid arthritis sera (23%). The extent of idiotypic sharing between BEG 2 and murine monoclonal DNA-binding antibodies, in particular monoclonal antibody (mAb) 423 (derived from a 15-day-old fetal MRL/Mp-lpr/lpr mouse) and mAb 402 (derived from an adult MRL/lpr mouse), was also investigated. Using a competition ELISA, it was shown that preincubation of BEG 2 with rabbit anti-423 and rabbit anti-402 inhibits the binding of BEG 2 to DNA, and the binding of 402 to DNA by anti-BEG 2 and anti-423. These data suggest that mAb BEG 2, 423 and 402 share common idiotypes, that autoreactivity is present in early fetal life, and that autoantibodies may be encoded for by germline genes, which have been conserved through evolution.
Watts
R A
RA
Department of Rheumatology Research, University College and Middlesex School of Medicine, London.
Ravirajan
C T
CT
Staines
N A
NA
Isenberg
D A
DA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D005333:Fetus / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M