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 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 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 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.