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 variabl e heavy chains were found to result from utilization of VH gene elemen ts that have been identified previously in other low-affinity anti-DNA s. These VH gene elements, VH26 and VH1.9III, are expressed in associa tion with different D gene-encoded CDR3s than in the other antibodies. The variable light chains were found to be encoded by VL gene element s 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 gen e elements that confer reactivity with DNA have been identified. Previ ous 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 l ow-affinity VHs, indicating that DNA is unlikely to be the driving ant igen. (C) 1996 Academic Press, Inc.