ArticleThe Journal of experimental medicine2002
Anti-DNA B cells in MRL/lpr mice show altered differentiation and editing pattern.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 100 citations in OpenAlex.
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- IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity.Clinical medicine insights. Pathology · 2016Review
- An entity evolving into a community: defining the common ancestor and evolutionary trajectory of chronic lymphocytic leukemia stereotyped subset #4.Molecular medicine (Cambridge, Mass.) · 2015Article
- Defects in Germinal Center Selection in SLE.Frontiers in immunology · 2015Review
- Positive selection of natural poly-reactive B cells in the periphery occurs independent of heavy chain allelic inclusion.PloS one · 2015Article
- TLR7 influences germinal center selection in murine SLE.PloS one · 2015Article
- CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow.The Journal of experimental medicine · 2014Article
- Contributions of B cells to lupus pathogenesis.Molecular immunology · 2014Review
- Dual immunoglobulin light chain B cells: Trojan horses of autoimmunity?Current opinion in immunology · 2014Review
- Temporal dynamics of clonal evolution in chronic lymphocytic leukemia with stereotyped IGHV4-34/IGKV2-30 antigen receptors: longitudinal immunogenetic evidence.Molecular medicine (Cambridge, Mass.) · 2013Article
- The Yaa locus and IFN-α fine-tune germinal center B cell selection in murine systemic lupus erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice.The Journal of experimental medicine · 2012Article
- Polyreactive antibodies in adaptive immune responses to viruses.Cellular and molecular life sciences : CMLS · 2012Review
- Caspase-activated DNase is required for maintenance of tolerance to lupus nuclear autoantigens.Arthritis and rheumatism · 2012Article
- Activation-induced deaminase-deficient MRL/lpr mice secrete high levels of protective antibodies against lupus nephritis.Arthritis and rheumatism · 2011Article
- B cell receptor editing in tolerance and autoimmunity.Annals of the New York Academy of Sciences · 2011Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have studied the regulation of anti-DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti-double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vkappa repertoire, but certain L chains, referred to as Vkappa editors, do not sustain dsDNA binding in combination with 3H9H/56R. In the nonautoimmune 3H9H/56R BALB/c, most B cells generated do not bind DNA because the transgene itself is edited or is associated with a Vkappa editor. A minor population of B cells (30%) bind dsDNA and express the lambda1 light chain (known to sustain 3H9H/56R DNA binding). These 3H9/56R/lambda1 B cells coexpress a kappa editor, and we propose that the down-regulation of the anti-DNA BCR caused by the dual L chain expression may prevent activation of this kappa/lambda population. These kappa/lambda B cells are sequestered in the marginal zone. Here, we studied the influence of autoimmunity on expression and regulation of 3H9H/56R. In 3H9H/56R MRL/lpr mice, the expression of anti-dsDNA is vastly accelerated. Anti-dsDNA B cells use noneditor kappas but, in addition, most anti-dsDNA B cells have edited the heavy chain transgene. lambda1 B cells (without the coexpression of a kappa editor) are found and the kappa/lambda1 MZ population is absent. Our results suggest that improper editing and failure to sequester autoreactive B cells may contribute to the breakdown of tolerance in MRL/lpr mice.
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