A NOVEL CLASS OF ANTI-DNA ANTIBODIES IDENTIFIED IN BALB/C MICE

We have characterized four IgG monoclonal antibodies (mAbs) derived from BALB/c mice that bind double-stranded DNA (dsDNA) with high affinity. The hydridomas were selected for expression of a member of the V(H)S107 family. Three of the four cell lines use the V(H)11 gene and one uses the V(H)1 gene. These antibodies exhibit many characteristics of pathogenic anti-DNA antibodies. They are high affinity and not broadly crossreactive. Unlike the anti-DNA antibodies in autoimmune mice, they exhibit no somatic mutation in their V(H) genes. These results demonstrate that somatic mutation of V(H)S107 genes is not necessary for generating high affinity dsDNA binding. The fact that such antibodies have not previously been reported suggests that they are rare and that their expression may be downregulated in both nonautoimmune and autoimmune individuals.