HUMAN B-CELL CLONES EXPRESSING LUPUS NEPHRITIS-ASSOCIATED ANTI-DNA IDIOTYPES ARE PREFERENTIALLY EXPANDED WITHOUT SOMATIC MUTATION

Human monoclonal anti-single/double-stranded (ss/ds) DNA antibodies (N E-1 and NE- 1 3) expressed cross-reactive idiotypes (Id), NE-1 Id, whi ch have been detected on the lupus glomeruli-deposited anti-DNA antibo dies. The nucleotide sequences of the variable regions of NE-1 and NE- 13 clones were analogous except for one nucleotide difference in the V (k) region. The V(H) and V(k) gene segments of NE-13 clone were identi cal with germline genes VH4.21 and Vb (or Vb'), respectively. CDR3s of NE-1 and NE-13 heavy chains were arginine rich and CDR1s contained an amino acid stretch, SGYY, the inverted sequence of YYGS, which was sh ared among CDR3s of several anti-DNA antibodies. Clonal frequency anal ysis using a limiting dilution method revealed that NE-1 Id-positive c lones at precursor cell level increased in lupus patients. These findi ngs suggest that some IgM anti-DNA clones which express NE-1 Id associ ated with lupus nephritis use germline genes without mutation and they may be preferentially expanded at the precursor cell levels as well a s at the mature cell level.