Linked Life Data

2118932

Source:http://linkedlifedata.com/resource/pubmed/id/2118932

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1990-10-17
pubmed:databankReference
pubmed:abstractText
Autoantibodies against thymocytes and RBC may contribute to the pathophysiology of homozygous viable motheaten (mev) autoimmune disease. Whether the production of these autoantibodies in mev mouse results from polyclonal nonspecific B cell activation or specific Ag-driven stimulation is not known. To understand the mechanisms involved in the induction of antithymocyte autoantibody response in mev mouse, we have studied the fine antigenic specificity, structure, and origin of three antithymocyte autoantibodies derived from mev splenic B cell hybridomas. Western blot analysis showed that these mAb bind to polypeptides of 33 and 105 kDa present in RBC and thymocytes, respectively. Additional specificities for the epitopes present in other polypeptides distinguished these three autoantibodies. Northern hybridization and flow microfluorimetry analysis indicated that these hybridomas are derived from the Ly1+ B cell subset. These autoreactive Ly-1 B cell hybridomas, chosen on the basis of their specificity, expressed L chain V genes from a single VK family (VK9) and VH genes from J606 and S107 families. Hybridomas UN34.11 and UN42.5 expressed the VK9 gene identical to that used by peritoneal Ly1+ B cells from various mouse strains and malignant B lymphoma cells secreting anti-mouse RBC treated with proteolytic enzyme bromelin and anti-SRBC antibodies. The third hybridoma, S2-14.2, used a VK9 gene identical to that expressed by MOPC41. None of the VK genes encoding these autoantibodies showed any somatic mutations. In the case of VH genes, the two hybridomas UN42.5 and S2-14.2 derived from two separate fusions, used identical VH genes from the J606 family. The third hybridoma UN34.11 used unmutated V11 germline VH gene, a member of the S107 family. Southern hybridizations, using oligonucleotide probes specific for CDR1 and CDR2, showed that the VH genes encoding the J606 autoantibodies were derived from a germline gene found in the 6.7-kb fragment of EcoRI-digested germline DNA. This germline VH gene is distinct from VH22.1 germline gene that codes for antigalactan antibodies. Sequence analysis of this gene showed perfect homology with the rearranged VH genes confirming the lack of somatic mutations. Thus, our data demonstrate that antithymocyte antibody response occurring in mev mouse is polyclonal and it involves Ly-1 B cells expressing unmutated germline VH and VK genes. These results indicate that antigen driven stimulation may not play an important role in the induction of anti-thymocyte antibody response in mev mouse.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
145
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2304-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:2118932-Animals, pubmed-meshheading:2118932-Antigens, Ly, pubmed-meshheading:2118932-Autoantibodies, pubmed-meshheading:2118932-B-Lymphocytes, pubmed-meshheading:2118932-Base Sequence, pubmed-meshheading:2118932-Blotting, Northern, pubmed-meshheading:2118932-Blotting, Southern, pubmed-meshheading:2118932-Erythrocytes, pubmed-meshheading:2118932-Genes, Immunoglobulin, pubmed-meshheading:2118932-Immunoglobulin Heavy Chains, pubmed-meshheading:2118932-Immunoglobulin Variable Region, pubmed-meshheading:2118932-Immunoglobulin kappa-Chains, pubmed-meshheading:2118932-Lymphocyte Activation, pubmed-meshheading:2118932-Mice, pubmed-meshheading:2118932-Mice, Mutant Strains, pubmed-meshheading:2118932-Molecular Sequence Data, pubmed-meshheading:2118932-Oligonucleotide Probes, pubmed-meshheading:2118932-Polymerase Chain Reaction, pubmed-meshheading:2118932-Thymus Gland
pubmed:year
1990
pubmed:articleTitle
Germline V genes encode viable motheaten mouse autoantibodies against thymocytes and red blood cells.
pubmed:affiliation
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't