Immunoglobulin (Ig) light chain repertoire has been implicated as a critical determinant in regulation of autoreactive B cells and production of pathogenic anti-DNA antibodies in systemic lupus erythematosus (SLE). We analyzed the impact of Ig λ chain repertoire on development of autoimmunity in patients with SLE.

We obtained genomic DNA from individual peripheral CD19+ B cells of 3 untreated active SLE patients, and amplified Vλ rearrangements from each single cell by polymerase chain reaction.

A total number of 208 VλJλ rearrangements were analyzed. Analyzed sequences included 158 productive rearrangements and 50 nonproductive rearrangements. The differences in Vλ gene usage in the productive and nonproductive repertoire of SLE patients were found compared to the non-autoimmune individuals. Vλ gene, 9A was significantly overrepresented in nonproducative repertoire of SLE patients (P=0.016). In the productive repertoire, Vλ genes, 3L and 1E were found more often in the SLE patients (P=0.001, P=0.043). When the productive and the nonproductive repertoires were compared, 9A was found significantly less in the productive repertoire in the SLE patients (P=0.000). There were no significant differences in the Jλ gene usage between SLE patients and non-autoimmune individuals, but Jλ2/3 gene was the most frequently used in SLE, whereas Jλ7 gene was the most frequently used in the normal subjects. In the productive SLE Vλ repertoire, 9.4% of the total sequences employed identical CDR3. It was particularly striking to find 7 identical versions of the 1G-Jλ2/3 VλJλ rearrangements from one patient and 3 of the same sequence from another patient. Notably, identical Vλ junctions in the SLE patients utilized significantly more homologous joining compared to Vλ junctions of the normal adults (P=0.044).

These data demonstrate regulation of λ light chain expression in the SLE patients by selection of unique Vλ genes. Also, biased selection and clonal expansion of particular Vλ rearrangements are apparent in the SLE λ repertoire.