VH and VL gene elements that encode human antibodies to DNA

We have determined the cDNA sequence of variable regions of heavy and light chains of three antibodies with low affinity to DNA. The variable heavy chains were found to result from utilization of VH gene elements that have been identified previously in other low-affinity anti-DNAs. These VH gene elements, VH26 and VH1.9III, are expressed in association with different D gene-encoded CDR3s than in the other antibodies. The variable light chains were found to be encoded by VL gene elements that have not previously been identified in anti-DNAs. The recurrent identification of only 10 germ line VH genes in 22 low-affinity anti-DNAs indicates that there is a high probability that all of the VH gene elements that confer reactivity with DNA have been identified. Previous studies have suggested that high-affinity antibodies to DNA result from an antigen-driven process of affinity maturation. However, only 6 of 13 high-affinity antibodies to DNA are derived from this set of low-affinity VHs, indicating that DNA is unlikely to be the driving antigen.