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 anlibodies (NE‐1 and NE‐13) expressed cross‐reactive idiotypes (Id), NE‐1 Id, which have been delected 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 V_k region. The V_H and V_k gene segments of NE‐13 clone were identical with germline genes VH4.21 and Vb(or Vb′). respectively. CDR3sof NE‐l 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.