Immunoglobulin V-lambda transcription profiling of systemic lupus erythematosus patients reveals biased usage of genes located near the Jλ-Cλ Segments

Abstract

To evaluate the distribution of usage and to quantify the transcription levels of the immunoglobulin lambda variable (IGLV) genes in patients with systemic lupus erythematosus (SLE) and normal individuals (NIs), cDNA samples from peripheral blood lymphocytes were prepared and probed with IGLV-specific oligonucleotides. Because recombinations involving V-lambda pseudogenes are nonproductive, we analysed the IGLV productive repertoire, as cDNAs were copied from IGLV mRNA producing B lymphocytes. Increased expression of the IGLV8a gene in SLE led us to analyse the transcription levels of all IGLV genes. We developed an expression profiling approach to scan the entire V-lambda locus on chromosome 22q11.2. The transcription profiling showed that usually the V-lambda genes located near the Jλ-Cλ cluster were preferentially expressed in both groups, i.e. patients and NIs, with the expression levels of SLE patients being significantly higher. However, genes displaying peaks of expression independent of Jλ-Cλ cluster proximity were observed along the IGLV locus. Our data permit us to conclude that there are differences in V-lambda gene expression between SLE patients and NIs, and a preferential usage of genes located near the Jλ-Cλ cluster. The data also demonstrate the occurrence of Vλ,-Jλ-Cλ-productive recombinations independent of gene localization along the locus.