Development of the B cell anti-DNA repertoire in (NZB x NZW)F sub(1) mice. Relationship with the natural autoimmune repertoire

The relationship between pathologic anti-DNA and natural autoantibodies (Auto Ab) remains unclear. In particular, it has not yet been elucidated whether pathologic anti-DNA antibodies originate from and are regulated by the pool of natural Auto Ab. To address this question, a large number of Ig-secreting hybridomas were derived from the unstimulated splenocytes of B/W mice, newborn to 12 mo of age, and their binding activities against a panel of self-Ag (DNA, actin, tubulin, myosin, and myoglobin), isotype, idiotypic determinants, and V sub(H) gene utilization were analyzed. The kinetics, immunochemical properties, and idiotypic analysis of polyspecific IgM mAb with DNA-binding activity strongly suggest that they belong to natural Auto Ab and constitute the precursors of pathologic IgG anti-DNA antibodies. In addition, an IgM polyspecific antibody was demonstrated to bind IgG anti-DNA mAb through F(ab') sub(2) interactions suggesting a regulatory role of natural antibodies and their participation in the control of pathologic Auto Ab production.