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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 Vλ 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. Vλ–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 1G 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.