Paul E, Diamond B
Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, New York 10461.
Autoimmunity. 1993;16(1):13-21. doi: 10.3109/08916939309010643.
Antibodies against double stranded DNA (dsDNA) are characteristic of systemic lupus erythematosus (SLE) and have been implicated in disease pathogenesis. Up to one third of an SLE patient's anti-dsDNA antibodies can express the lambda L chain idiotype 8.12. Serum titers of this idiotype are elevated in 50% of SLE patients, and idiotypic antibodies are present in glomerular immune deposits associated with lupus nephritis. Two EBV transformed B cell lines, KS3 from a patient with SLE and SD6 from an individual without autoimmune disease, secrete 8.12+ IgG antibodies that bind dsDNA. The 8.12+ lambda L chains of these anti-DNA antibodies are encoded by members of the V lambda II gene family; the KS3 heavy chain is encoded by a VH4-DM1-DQ52-JH6b-C gamma 1 gene rearrangement and the SD6 heavy chain is encoded by a VH3-D21/9-JH6b-C gamma 1 rearrangement. Both of these monoclonal antibodies are somatically mutated: the KS3 antibody displays mutations in complementarity determining regions (CDRs) and the SD6 antibody in framework regions (FRs). The significance of these different patterns of mutation in two potentially pathogenic anti-DNA antibodies is discussed.
抗双链DNA（dsDNA）抗体是系统性红斑狼疮（SLE）的特征性抗体，并与疾病发病机制有关。高达三分之一的SLE患者的抗dsDNA抗体可表达λ轻链独特型8.12。50%的SLE患者中该独特型的血清滴度升高，且独特型抗体存在于与狼疮性肾炎相关的肾小球免疫沉积物中。两个EB病毒转化的B细胞系，来自一名SLE患者的KS3和来自一名无自身免疫性疾病个体的SD6，分泌结合dsDNA的8.12+ IgG抗体。这些抗DNA抗体的8.12+λ轻链由VλII基因家族成员编码；KS3重链由VH4-DM1-DQ52-JH6b-Cγ1基因重排编码，SD6重链由VH3-D21/9-JH6b-Cγ1重排编码。这两种单克隆抗体均发生体细胞突变：KS3抗体在互补决定区（CDR）显示突变，SD6抗体在框架区（FR）显示突变。本文讨论了这两种潜在致病性抗DNA抗体中不同突变模式的意义。
