The V_λ-J_λ repertoire of patients with systemic lupus erythematosus manifests characteristics of the natural antibody repertoire

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 V_λ repertoire in SLE patients. Methods. The SLE V_λ repertoire of B cells obtained from 3 SLE patients was analyzed and compared in detail with the V_λ 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-J_λ rearrangements were amplified from the genomic DNA of individual B cells by polymerase chain reaction. Results. The expressed V_λ repertoire of SLE patients contained several similarities with the expressed repertoire of the fetus and the adult CD5+ B cells. The V_λ 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 V_λ 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 V_λ clones utilized homology-mediated joining at the V_λ-J_λ junctions. Conclusion. These data demonstrate that the SLE V_λ-J_λ 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.