The V(lambda)-J(lambda) 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(lambda) repertoire and compared it with the V(lambda) repertoire in SLE patients.


METHODS
The SLE V(lambda) repertoire of B cells obtained from 3 SLE patients was analyzed and compared in detail with the V(lambda) 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(lambda)-J(lambda) rearrangements were amplified from the genomic DNA of individual B cells by polymerase chain reaction.


RESULTS
The expressed V(lambda) repertoire of SLE patients contained several similarities with the expressed repertoire of the fetus and the adult CD5+ B cells. The V(lambda) 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(lambda) 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(lambda) clones utilized homology-mediated joining at the V(lambda)-J(lambda) junctions.


CONCLUSIONS
These data demonstrate that the SLE V(lambda)-J(lambda) 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.
Lee
Jisoo
J
Ewha Women's University College of Medicine, Seoul, South Korea.
Cho
Young Joo
YJ
Lipsky
Peter E
PE
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D016133:Polymerase Chain Reaction
D001323:Autoantibodies; D007144:Immunoglobulin J-Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; C030566:immunoglobulin light chain protein Sm lambda