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 x NZW)F1 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 x NZW)F1 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 x NZW)F1 mice would appear to derive from the selective oligoclonal expansion of selected B cells that express such structures.