Publication Date:
2006-05-20
Description:
Antibodies against nuclear self-antigens are characteristic of systemic autoimmunity, although mechanisms promoting their generation and selection are unclear. Here, we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus are intrinsically biased toward nucleolar antigens because of increased expression of TLR7, a single-stranded RNA-binding innate immune receptor. The TLR7 gene is duplicated in Yaa mice because of a 4-Megabase expansion of the pseudoautosomal region. These results reveal high divergence in mouse Y chromosomes and represent a good example of gene copy number qualitatively altering a polygenic disease manifestation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pisitkun, Prapaporn -- Deane, Jonathan A -- Difilippantonio, Michael J -- Tarasenko, Tatyana -- Satterthwaite, Anne B -- Bolland, Silvia -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2006 Jun 16;312(5780):1669-72. Epub 2006 May 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Rockville, MD 20852, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16709748" target="_blank"〉PubMed〈/a〉
Keywords:
Aminoquinolines/pharmacology
;
Animals
;
Antibodies, Antinuclear/biosynthesis/immunology
;
Antibody Specificity
;
Autoimmunity/*genetics
;
B-Lymphocytes/*immunology
;
Cell Nucleolus/*immunology
;
Female
;
Gene Dosage
;
*Gene Duplication
;
In Situ Hybridization, Fluorescence
;
Lupus Erythematosus, Systemic/genetics/immunology
;
Lymphocyte Activation
;
Male
;
Membrane Glycoproteins/*genetics/immunology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Inbred Strains
;
Oligonucleotide Array Sequence Analysis
;
Protein-Tyrosine Kinases/genetics/metabolism
;
RNA/*immunology
;
Receptors, Antigen, B-Cell/immunology
;
Toll-Like Receptor 7/*genetics/immunology
;
X Chromosome/genetics
;
Y Chromosome/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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