Irigoyen M, Manheimer-Lory A, Gaynor B, Diamond B
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
J Clin Invest. 1994 Aug;94(2):532-8. doi: 10.1172/JCI117366.
The 8.12 idiotype characterizes a subpopulation of anti-DNA antibodies in patients with systemic lupus erythematosus (SLE). The idiotype is present on lambda light chains and has previously been shown to be exclusively encoded by V lambda II light chains. RFLP analysis of the V lambda II gene family has shown the family to consist of 10 to 15 members. Thus far, the sequences of seven V lambda II germline genes are reported in the literature with one of these a pseudogene. To identify the V lambda II genes that encode 8.12 positive antibodies and to further characterize the V lambda II family, germline V lambda II clones were derived from a patient with SLE. Two libraries were constructed: a genomic DNA library and a library of PCR-derived V lambda II gene products obtained using a conserved V lambda II leader region primer and a primer for the nonamer region 3' of the coding sequence. We now describe seven new germline genes, two of which are pseudogenes. Comparison of V lambda II germline genes to sequences of 8.12 positive light chains produced by EBV-transformed B cell lines show that all 8.12 positive light chains are encoded by a limited number of highly homologous members of the V lambda II family. 8.12 negative V lambda II encoded light chains also derive from a limited number of V lambda II genes, suggesting that only a subset of the apparently available V lambda II genes are commonly expressed.
8.12独特型可表征系统性红斑狼疮（SLE）患者体内抗DNA抗体的一个亚群。该独特型存在于λ轻链上，先前已证明其仅由VλII轻链编码。对VλII基因家族的限制性片段长度多态性（RFLP）分析表明，该家族由10至15个成员组成。到目前为止，文献中报道了7个VλII种系基因的序列，其中一个是假基因。为了鉴定编码8.12阳性抗体的VλII基因，并进一步表征VλII家族，从一名SLE患者中获得了种系VλII克隆。构建了两个文库：一个基因组DNA文库和一个使用保守的VλII前导区引物和编码序列3'端九聚体区域的引物获得的PCR衍生VλII基因产物文库。我们现在描述7个新的种系基因，其中两个是假基因。将VλII种系基因与EB病毒转化的B细胞系产生的8.12阳性轻链的序列进行比较，结果表明，所有8.12阳性轻链均由VλII家族中数量有限的高度同源成员编码。8.12阴性的VλII编码轻链也来自数量有限的VλII基因，这表明在明显可用的VλII基因中，只有一个子集通常会表达。
