Differences in Vϰ gene utilization and VH CDR3 sequence among anti‐DNA from C3H‐lpr mice and lupus mice with nephritis

To investigate the molecular properties of anti‐DNA from lpr mice that express high levels of anti‐DNA without immune‐mediated nephritis, the sequences of VH and Vϰ genes encoding 11 monoclonal anti‐DNA antibodies derived from C3H‐lpr/lpr (C3H‐lpr) mice were studied. All of the C3H‐lpr monoclonal anti‐DNA bound single‐stranded DNA while five also bound double‐stranded DNA. Two of the hybridomas were clonally related as determined by Southern analysis and sequencing. Sequence analysis of C3H‐lpr anti‐DNA revealed the use of VH genes that encode anti‐DNA from the MRL‐lpr/lpr and (NZB X NZW)F1 mouse models of lupus, although differences occurred in the VH CDR3 amino acid content. In contrast, the Vϰ genes from C3H‐lpr mice lacked significant identity with previously reported Vϰ genes for anti‐DNA from lupus models. These results indicate that anti‐DNA from C3H‐lpr mice differ from anti‐DNA from lupus mice with nephritis in patterns of V gene expression and suggest a molecular basis for the lack of pathogenicity of anti‐DNA in these mice.