MOLECULAR ANALYSIS OF THE HUMAN-IMMUNOGLOBULIN V-LAMBDA-II GENE FAMILY

The 8.12 idiotype characterizes a subpopulation of anti-DNB antibodies in patients with systemic lupus erythematosus (SLE). The idiotype is present on lambda light chains and has previously been shown to be exc lusively encoded by V lambda II light chains. RFLP analysis of the V l ambda II gene family has shown the family to consist of 10 to 15 membe rs. Thus far, the sequences of seven V lambda II germline genes are re ported in the literature with one of these a pseudogene. To identify t he V lambda II genes that encode 8.12 positive antibodies and to furth er characterize the V lambda II family, germline V lambda II clones we re derived from a patient with SLE. Two libraries were constructed: a genomic DNA library and a library of PCR-derived V lambda II gene prod ucts obtained using a conserved V lambda II leader region primer and a primer for the nonamer region 3' of the coding sequence. We now descr ibe seven new germline genes, two of which are pseudogenes. Comparison of V lambda II germline genes to sequences of 8.12 positive light cha ins produced by EBV-transformed B cell lines show that all 8.12 positi ve light chains are encoded by a limited number of highly homologous m embers of the V lambda II family. 8.12 negative V lambda lI encoded li ght chains also derive from a limited number of V lambda II genes, sug gesting that only a subset of the apparently available V lambda II gen es are commonly expressed.