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The systemic lupus erythematosus VλJλ repertoire harbors characteristics of the natural antibody repertoire
Arthritis Res Ther volume 5, Article number: 150 (2003)
The molecular mechanisms that lead to autoantibody production in systemic lupus erythematosus (SLE) are poorly understood. There is evidence that pathogenic IgG autoantibodies characteristic of human SLE may arise from the physiologically autoreactive natural antibody repertoire of fetal or CD5+B cells. To address this hypothesis, the SLE Vλ repertoire obtained from B cells of three SLE patients was analyzed and compared in detail with the Vλ repertoire obtained from IgM+ B cells of three human fetal spleens and IgM+CD5+/CD5- B cells of two normal adults. VλJλ rearrangements were amplified from genomic DNA of individual B cells by PCR. The expressed Vλ repertoire of SLE patients contained several similarities with the expressed repertoire of the fetal and adult CD5+ B cells. The Vλ gene, 1G, was a major component of the SLE, fetal and adult CD5+B-cell repertoire, but not in the adult CD5- B-cell population. The restriction of junctional diversity by utilization of homology-directed joining (H-joining) together with the absence of N-regions was a prominent feature of the fetal and adult CD5+ B-cell repertoires. This restriction was also observed in the SLE repertoire, but was less significant in the adult CD5- B-cell population. Furthermore, profound expansion of Vλ clones employing identical CDR3s were observed in the adult CD5+ B cells, the fetal cells, and the SLE repertoire, whereas the frequency of the Vλ clones were much lower in the adult CD5- B-cell population. Notably, significant numbers of expanded adult CD5+ B cells, and fetus and SLE Vλ clones utilized H-joining at the junctions. These data demonstrate that the SLE VλJλ repertoire harbors characteristics of the natural antibody repertoire. These observations imply that the fetal antibody repertoire with restricted antigen specificities can be conserved through development via CD5+ B cells, and during abnormal immune responses can potentially give rise to SLE-associated pathogenic autoantibodies.
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Lee, J., Lipsky, P. The systemic lupus erythematosus VλJλ repertoire harbors characteristics of the natural antibody repertoire. Arthritis Res Ther 5 (Suppl 3), 150 (2003). https://doi.org/10.1186/ar951