Antibodies binding to double-stranded (ds) DNA are strongly associated with @entity8 in @entity1 with @entity1252 ( @entity1252 ). We have generated two new IgG DNA-binding monoclonal antibodies (mAb), RH-14 and DIL-6, from the peripheral blood lymphocytes of two @entity1252 @entity1 with @entity631 using the heteromyeloma cell line CB-F7. RH-14 is an IgG1 lambda antibody which also bound to single-stranded DNA, histones and nucleosomes. DIL-6 is an @entity3172 lambda antibody with restricted antigen binding specificity. cDNA encoding the variable regions of the heavy (V(H)) and light (V(L)) chains of RH-14 was sequenced and the antigen binding site of this mAb was computer modelled. Sequence analysis of V(H) and V(L) regions of RH-14 showed that V(H) is derived from germ-line gene V3-7, a member of the V(H)3 family, and V(L) is derived from @entity31720 , a member of the V(lambda)2 family. Somatic mutations and basic @entity535 residues are identified in the complementarity-determining regions of both V(H) and V(L) regions. The nephritogenic properties of these mAb were analyzed by implanting and growing the hybridoma cells secreting the mAb in the peritoneum of @entity915 @entity19 . The animals that received the RH-14 hybridoma produced higher levels of @entity644 (3 to > or = 4) (p < 0.001) compared to the groups that received DIL-6 (trace to > or = 1) or CB-F7 (trace). Electron microscopy of kidney sections from all the RH-14-implanted animals showed granular immunoglobulin deposition in the renal glomerular capillaries and mesangium. In this study we have shown for the first time using electron microscopy that a human IgG anti-dsDNA mAb, RH-14, is nephritogenic and that deposition of such an antibody alone is sufficient to induce @entity8 .

Genetic, structural and functional properties of an IgG DNA-binding monoclonal antibody from a lupus XXXX with nephritis.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity644 :: ('MESH:D011507', 'Disease') :: ['proteinuria'] @entity8 :: ('MESH:D007674', 'Disease') :: ['renal involvement', 'renal damage'] @entity3172 :: ('3502', 'Gene') :: ['IgG3'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity31720 :: ('8701', 'Gene') :: ['DPL 11'] @entity1252 :: ('MESH:D008180', 'Disease') :: ['SLE', 'systemic lupus erythematosus'] @entity915 :: ('MESH:D053632', 'Disease') :: ['SCID'] @entity631 :: ('MESH:D005921', 'Disease') :: ['glomerulonephritis']
@entity1 :: (9606,Species) :: ['patient']
