ArticleThe Journal of clinical investigation1996
Characterization of a germline Vk gene encoding cationic anti-DNA antibody and role of receptor editing for development of the autoantibody in patients with systemic lupus erythematosus.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 73 citations in OpenAlex.
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- Construction of a Prognostic Immune Signature for Squamous-Cell Lung Cancer to Predict Survival.Frontiers in immunology · 2020Article
- Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies.Immunological reviews · 2019Review
- Article
- Immunological aspects in chronic lymphocytic leukemia (CLL) development.Annals of hematology · 2012Review
- The establishment of early B cell tolerance in humans: lessons from primary immunodeficiency diseases.Annals of the New York Academy of Sciences · 2011Review
- B cell receptor editing in tolerance and autoimmunity.Annals of the New York Academy of Sciences · 2011Review
- Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Reduced receptor editing in lupus-prone MRL/lpr mice.The Journal of experimental medicine · 2007Article
- Interleukin-6 is responsible for aberrant B-cell receptor-mediated regulation of RAG expression in systemic lupus erythematosus.Immunology · 2007Article
- B cells in autoimmune diseases: insights from analyses of immunoglobulin variable (Ig V) gene usage.Autoimmunity reviews · 2007Review
- Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Impaired early B cell tolerance in patients with rheumatoid arthritis.The Journal of experimental medicine · 2005Article
- Defective B cell tolerance checkpoints in systemic lupus erythematosus.The Journal of experimental medicine · 2005Article
- Recombination activating genes (RAG) induce secondary Ig gene rearrangement in and subsequent apoptosis of human peripheral blood circulating B lymphocytes.Clinical and experimental immunology · 2004Article
- Molecular determinants of the human antibody response to HIV-1: implications for disease control.Journal of clinical immunology · 2001Article
- Perturbations in the impact of mutational activity on Vlambda genes in systemic lupus erythematosus.Arthritis research · 2001Article
- Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci.Infection and immunity · 2000Article
- Immunoglobulin kappa chain receptor editing in systemic lupus erythematosus.The Journal of clinical investigation · 1998Article
- Lupus-specific antibodies reveal an altered pattern of somatic mutation.The Journal of clinical investigation · 1997Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We found previously that cationic anti-DNA autoantibodies (autoAbs) have nephritogenic potential and usage of a specific germline Vk gene, A30, has major influences on cationic charge of the autoAb in human lupus nephritis. In the present study, we have characterized A30 germline Vk gene using cosmid cloning technique in patients with SLE. A30 gene locus locates in less than 250 kb from the Ck region, and the cationic anti-DNA mRNA used the upstream Jk2 gene, indicating that cationic anti-DNA mRNA is a product of primary gene rearrangement. By using PCR technique, we found that A30 gene locus in the genome was defective in eight out of nine SLE patients without nephritis. In contrast, all nine patients with lupus nephritis had intact A30 gene. The presence and absence of A30 gene was associated with the development of lupus nephritis or not (P < 0.01, by Fisher's exact test, two-sided). It was thus suggested that absence of functional A30 gene may rescue from developing lupus nephritis in the patients. A30 is reported to be a potentially functional but rarely expressed Vk gene in humans. It is possible that normal B cells edit primarily rearranged A30 gene with autoreactive potentials by receptor editing mechanism for changing the affinity of the B cell Ag receptor to avoid self-reactivity, whereas SLE B cells may have a defect in this mechanism. Indeed, we found that normal B cells edit A30-Jk2 gene in their genome possibly by inversion mechanism, whereas SLE B cells contain rearranged A30-Jk2-Ck gene in the genome and express A30-associated mRNA, suggesting that receptor editing mechanism is also defective in patients with SLE. Our study suggests that polymorphism of Ig Vk locus, and failure of receptor editing may contribute to the development of pathogenic anti-DNA responses in humans.
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