V gene analysis of anti-cardiolipin antibodies from (NZW x BXSB) F1 mice.
In (NZW x BXSB) F1 (W/B F1) male mice, systemic lupus-like disease, thrombocytopenia and coronary vascular disease with myocardial infarction occur, due to the presence of platelet-associated antibodies, anti-platelet antibodies and anti-cardiolipin antibodies (aCL). We developed monoclonal aCL and analysed the specificity of aCL. In the W/B F1 mice, there are aCL with pathogenic properties, which have an IgG isotype and reveal a cofactor-dependent binding to CL, binding activity to platelets, and lupus anti-coagulant (LA) activity. Here, we analysed the usage of VH and V kappa genes of six aCL, including two pathogenic aCL, from W/B F1 mice, in an attempt to address the question of whether or not aCL with pathogenic properties use restricted Ig V genes. Sequence analysis of VH and V kappa genes of aCL showed that the pathogenic aCL had VHJ558 and V kappa 21 or V kappa 23 genes, whereas the other aCL without pathogenic features used mainly the 7183 VH family and the random V kappa gene group. However, two pathogenic aCL showed a 86.6% homology with the IgV region, each other, indicating that they were not closely related clones. Thus, these findings suggest the possibility that usage of Ig VH genes in pathogenic aCL is not random, but that there may exist a few epitopes of antigen recognized by the pathogenic aCL.
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Y
Y
Kita
T
T
Sumida
I
I
Iwamoto
S
S
Yoshida
T
T
Koike
D000595:Amino Acid Sequence; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000235:genetics* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics*; D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D017153:Antibodies, Anticardiolipin; D002308:Cardiolipins; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D004247:DNA