Comparison of the Frequencies of Arginines in Heavy Chain CDR3 of Antibodies Expressed in the Primary B‐Cell Repertoires of Autoimmune‐Prone and Normal Mice

Because the pathogenesis of anti‐DNA Ab in SLE is correlated to Ab specificity for native DNA (dsDNA), understanding how such specificity is generated is important. The VH structures of most autoimmune anti‐DNA antibodies include at least one arginine in VH–CDR3; moreover, antibody specificity for dsDNA can be correlated to the relative position of arginines in VH–CDR3. The coding sequences for most VH–CDR3 arginines among the anti‐DNA MoAbs we have studied to date appeared to have been encoded by sequences generated during V–D–J recombination and would have been expressed in the primary B‐cell repertoire. The frequency at which arginine codons are generated during V–D–J recombination therefore could potentially influence the frequency at which DNA‐specific B cells are generated in the primary B‐cell repertoire. The present study was undertaken to determine whether a higher percentage of B cells in the primary, preautoimmune repertoire of autoimmune‐prone (NZB × NZW)F 1 mice have immunoglobulin heavy chains with at least one VH–CDR3 arginine compared to B cells in the primary, preimmune repertoire of non‐autoimmune‐prone BALB/c mice. The present results indicate that mature B cells in preautoimmune (NZB × NZW)F 1 mice, whether specific for DNA or not, are no more likely to have heavy chains with VH–CDR3 arginines than are B cells in BALB/c mice. The high frequency of recurrence of VH–CDR3 arginines among autoimmune anti‐DNA in (NZB × NZW)F 1 mice would appear to derive from the selective oligoclonal expansion of selected B cells that express such structures.