Human B-cell clones expressing lupus nephritis-associated anti-DNA idiotypes are preferentially expanded without somatic mutation.

Abstract

Human monoclonal anti-single/double-stranded (ss/ds) DNA antibodies (NE-1 and NE-13) expressed cross-reactive idiotypes (Id), NE-1 Id, which have been detected on the lupus glomeruli-deposited anti-DNA antibodies. The nucleotide sequences of the variable regions of NE-1 and NE-13 clones were analogous except for one nucleotide difference in the Vk region. The VH and Vk gene segments of NE-13 clone were identical 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 shared among CDR3s of several anti-DNA antibodies. Clonal frequency analysis using a limiting dilution method revealed that NE-1 Id-positive clones at precursor cell level increased in lupus patients. These findings suggest that some IgM anti-DNA clones which express NE-1 Id associated with lupus nephritis use germline genes without mutation and they may be preferentially expanded at the precursor cell levels as well as at the mature cell level.