Linked Life Data

7673734

Source:http://linkedlifedata.com/resource/pubmed/id/7673734

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1995-10-16
pubmed:abstractText
Anti-DNA Ab are strictly regulated, except in autoimmunity, where they are expressed and may contribute to pathogenicity. To study constitutive anti-DNA Ab secretion in nonautoimmune mice, two anti-dsDNA H/L chain transgene combinations were constructed using an IgG2b C region with secretory but no transmembrane domain exons. One H/L combination, consisting of the VH3H9 H and V kappa 4 L chain transgenes, was chosen to recreate 3H9, an autoantibody that originally arose in an autoimmune MRL/lpr mouse; the other paired a higher affinity variant of VH3H9, 56R, with the same V kappa 4 L chain. Elevated titers of IgG2b along with normal levels of other isotypes were observed in transgene-positive mice, indicating that constitutive transgene-directed Ab secretion was achieved. Sera and hybridoma supernatants from VH3H9 gamma transgene-positive animals exhibited binding to dsDNA, ssDNA, and cardiolipin. Mice expressing the 56R gamma H chain and the V kappa 4 L chain showed enhanced binding. Expression of the transgenes correlated with signs of autoimmune disease, including prolonged plasma clotting in vitro, and reduced litter size. The results suggest that even a single autoreactive H chain that escapes tolerance may suffice to induce features of autoimmune disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
155
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3213-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Constitutive secretion of transgene-encoded IgG2b autoantibodies leads to symptoms of autoimmune disease.
pubmed:affiliation
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't