The Vλ-Jλ repertoire of patients with systemic lupus erythematosus manifests characteristics of the natural antibody repertoire

Abstract

Objective. To understand in detail the mechanisms of autoantibody production in patients with systemic lupus erythematosus (SLE), we performed a comprehensive analysis of the normal human immunoglobulin light chain V λ repertoire and compared it with the Vλ repertoire in SLE patients. Methods. The SLE Vλ repertoire of B cells obtained from 3 SLE patients was analyzed and compared in detail with the Vλ repertoire of IgM+ B cells obtained from 3 human fetal spleens and IgM+, CD5+ B cells obtained from 2 normal adults. Conventional IgM+, CD5- B cells obtained from normal adults were used as controls. V λ-Jλ rearrangements were amplified from the genomic DNA of individual B cells by polymerase chain reaction. Results. The expressed Vλ repertoire of SLE patients contained several similarities with the expressed repertoire of the fetus and the adult CD5+ B cells. The Vλ genes 3L and IG were overexpressed in the fetus, the adult CD5+ B cells, and the patients with SLE. The selection for rearrangements with restricted junctional diversity by utilization of homology-mediated joining, together with diminished N nucleotide addition, was a prominent feature of fetal, adult CD5+, and SLE B cell repertoires. Furthermore, profound expansion of Vλ clones with identical third complementarity-determining regions was observed in the adult CD5+, fetal, and SLE B cell repertoires. Notably, significant numbers of expanded adult CD5+ B cells, fetal, and SLE Vλ clones utilized homology-mediated joining at the Vλ-Jλ junctions. Conclusion. These data demonstrate that the SLE Vλ-Jλ repertoire manifests characteristics of normal adult IgM+,CD5+ and fetal B cell populations that are known to be enriched for the production of natural autoantibodies.