| Vkappa polymorphisms in NOD mice are spread throughout the entire immunoglobulin kappa locus and are shared by other autoimmune strains. | |
| | |
MedLine Citation:
|
PMID: 20556377 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The diversity of immunoglobulin (Ig) and T cell receptor (TCR) genes available to form the lymphocyte repertoire has the capacity to produce a broad array of both protective and harmful specificities. In type 1 diabetes (T1D), the presence of antibodies to insulin and other islet antigens predicts disease development in both mice and humans, and demonstrate that immune tolerance is lost early in the disease process. Anti-insulin T cells isolated from T1D-prone non-obese diabetic (NOD) mice use polymorphic TCRalpha chains, suggesting that the available T cell repertoire is altered in these autoimmune mice. To probe whether insulin-binding B cells also possess polymorphic V genes, Ig light chains were isolated and sequenced from NOD mice that harbor an Ig heavy chain transgene. Three insulin-binding Vkappa genes were identified, all of which were polymorphic to the closest germline sequence matches present in the GenBank database. Additional analysis of over 300 light chain sequences from multiple sources, including germline DNA, shows that polymorphisms are spread throughout the entire NOD Igkappa locus, as these polymorphic sequences represent 43 distinct Vkappa genes which belong to 14 Vkappa families. Database searches reveal that a majority of polymorphic Vkappa genes identified in NOD are identical to Vkappa genes isolated from SLE-prone NZBxNZW F1 or MRL strains of mice, suggesting that a shared Igkappa haplotype may be present. Predicted amino acid changes preferentially occur in CDR, and thus could alter antigen recognition by the germline B cell repertoire of autoimmune versus non-autoimmune mouse strains. |
| | |
Authors:
|
Rachel A Henry; Peggy L Kendall; Emily J Woodward; Chrys Hulbert; James W Thomas |
Related Documents
:
|
15153497 - Characterization of the human ig heavy chain antigen binding complementarity determinin... 3937727 - Light chain germ-line genes and the immune response to 2-phenyloxazolone. 6190167 - Structural bases for public idiotypic specificities of monoclonal antibodies directed a... 12551847 - Cloning of shark rag2 and characterization of the rag1/rag2 gene locus. 11997097 - Genomic organization of the gene that encodes the precursor to egf-related peptides, ex... 9746557 - Dna sequencing and analysis of the low-ca2+-response plasmid pcd1 of yersinia pestis kim5. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-17 |
Journal Detail:
|
Title: Immunogenetics Volume: 62 ISSN: 1432-1211 ISO Abbreviation: Immunogenetics Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-07-27 Completed Date: 2010-08-20 Revised Date: 2010-12-03 |
Medline Journal Info:
|
Nlm Unique ID: 0420404 Medline TA: Immunogenetics Country: United States |
Other Details:
|
Languages: eng Pagination: 507-20 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Division of Rheumatology, Vanderbilt University, Nashville, TN, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Substitution Animals Autoimmunity / genetics* B-Lymphocytes / immunology Base Sequence DNA Primers / genetics Diabetes Mellitus, Type 1 / genetics, immunology Genes, Immunoglobulin Heavy Chain Genes, Immunoglobulin Light Chain* Immunoglobulin Variable Region / genetics Immunoglobulin kappa-Chains / genetics* Insulin / immunology Mice Mice, Inbred NOD Mice, Transgenic Molecular Sequence Data Polymorphism, Genetic* Sequence Homology, Nucleic Acid Species Specificity T-Lymphocytes / immunology |
| Grant Support | |
ID/Acronym/Agency:
|
5 T32 GM08554/GM/NIGMS NIH HHS; 5 T32 HL069765/HL/NHLBI NIH HHS; AI051448/AI/NIAID NIH HHS; CA68485/CA/NCI NIH HHS; DK058404/DK/NIDDK NIH HHS; DK20593/DK/NIDDK NIH HHS; HL65962/HL/NHLBI NIH HHS; K08 DK070924/DK/NIDDK NIH HHS; P30 CA68485/CA/NCI NIH HHS; R01 AI051448-07/AI/NIAID NIH HHS; R01 AI051448-08/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/DNA Primers; 0/Immunoglobulin Variable Region; 0/Immunoglobulin kappa-Chains; 11061-68-0/Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Intestinal microbiota diversity of the flat fish Solea senegalensis (Kaup, 1858) following probiotic...
Next Document: Proteomic analysis of mineralising osteoblasts identifies novel genes related to bone matrix mineral...