Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-6-13
pubmed:abstractText
Terminal deoxynucleotidyl transferase (TdT) places non-template-coded nucleotides (N additions) in the VH CDR3 of T cell receptors and immunoglobulins. Amino acids coded for by N additions are important in autoantibody binding of dsDNA in lupus. We hypothesized that a genetic lack of TdT would modulate disease in lupus-prone mice. To test this hypothesis, we derived TdT-deficient MRL/lpr mice. Serum levels of anti-dsDNA antibodies and anti-dsDNA producing splenocytes were significantly lower in the TdT(-) versus TdT(+) littermates. Albuminuria, glomerular IgG deposition, and pathologic renal disease were significantly reduced in the TdT(-) mice. Sequence analysis of anti-dsDNA hybridomas derived from TdT(-) mice revealed a lack of N additions, short VH CDR3 segments, yet the presence of VH CDR3 arginines. Thus, the genetic absence of TdT reduces autoantibody production and clinical disease in MRL/lpr mice, confirming the importance of N additions in the autoimmune response in these mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1521-6616
pubmed:author
pubmed:issnType
Print
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
186-97
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12804532-Albuminuria, pubmed-meshheading:12804532-Animals, pubmed-meshheading:12804532-Antibodies, pubmed-meshheading:12804532-Autoantibodies, pubmed-meshheading:12804532-B-Lymphocytes, pubmed-meshheading:12804532-Base Sequence, pubmed-meshheading:12804532-Biological Markers, pubmed-meshheading:12804532-DNA Nucleotidylexotransferase, pubmed-meshheading:12804532-Glomerulonephritis, pubmed-meshheading:12804532-Immunoglobulin G, pubmed-meshheading:12804532-Joint Diseases, pubmed-meshheading:12804532-Joints, pubmed-meshheading:12804532-Kidney, pubmed-meshheading:12804532-Kidney Diseases, pubmed-meshheading:12804532-Lung, pubmed-meshheading:12804532-Lung Diseases, pubmed-meshheading:12804532-Mice, pubmed-meshheading:12804532-Mice, Inbred MRL lpr, pubmed-meshheading:12804532-T-Lymphocytes
pubmed:year
2003
pubmed:articleTitle
Effect of genetic deficiency of terminal deoxynucleotidyl transferase on autoantibody production and renal disease in MRL/lpr mice.
pubmed:affiliation
Medical Research Service, Ralph H. Johnson VAMC, and the Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. gilkeson@musc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't