02698nas a2200313   4500000000100000008004100001260001600042653002800058653001800086653002600104653001100130653001500141653003200156653003500188653001200223653003400235653002800269653001900297653003600316100001800352700001700370700001600387700001600403245011300419300001300532490000800545520181700553022001402370       1987                            d  c1987 Oct 0110aAntibodies, Antinuclear10aBase Sequence10aGenes, Immunoglobulin10aHumans10aHybridomas10aImmunoglobulin Heavy Chains10aImmunoglobulin Variable Region10aleprosy10aLupus Erythematosus, Systemic10aMolecular Sequence Data10aRNA, Messenger10aSequence Homology, Nucleic Acid1 aDersimonian H1 aSchwartz R S1 aBarrett K J1 aStollar B D00aRelationship of human variable region heavy chain germ-line genes to genes encoding anti-DNA autoantibodies.  a2496-5010 v1393 a<p>In order to identify the V region genes encoding systemic lupus erythematosus (SLE)-derived anti-DNA autoantibodies, we have determined the nucleotide sequence of heavy chain mRNA from several DNA-binding immunoglobulins secreted by human hybridomas. We used the technique of cDNA primer extension for determining sequences of the VH, D, and JH gene segments of anti-DNA autoantibodies from three different primary hybridoma growths from an SLE patient and one hybridoma from a leprosy patient. Immunoglobulins from two of the SLE hybridomas expressed the same idiotype, Id-16/6, which is also expressed on immunoglobulins in sera of patients with active SLE. Their mRNA sequences showed complete homology to each other in the V, D, and J genes and more than 99% homology to the VH26 germ-line gene sequence, a member of the human VHIII gene family. The VH mRNA sequence of the third SLE hybridoma, 21/28, which was idiotypically unrelated to the other two, was 93% homologous to a different VH germ-line gene sequence, HA2, a member of the human VHI gene family. The fourth anti-DNA-producing hybridoma, 8E10, was derived from a leprosy patient of different ethnic origin than the SLE patient. It was idiotypically related to 21/28 and expressed a VH segment gene identical to that of 21/28. Hybridomas 21/28 and 8E10 shared sequence homology with the VH26 anti-DNA antibodies in the first complementarity-determining region. In addition, 21/28 shared sequence homology with the Id-16/6+ group in the region encoded by the D and J gene segments. Our findings indicate that some SLE autoantibodies are encoded by unmodified or scarcely modified VH germ-line genes that are conserved in the human population and identify two distinct VH germ-line genes that can encode segments of anti-DNA immunoglobulins.</p>  a0022-1767