Regulation of B cell tolerance by the lupus susceptibility gene Ly108 - PubMed (original) (raw)
. 2006 Jun 16;312(5780):1665-9.
doi: 10.1126/science.1125893.
Affiliations
- PMID: 16778059
- DOI: 10.1126/science.1125893
Regulation of B cell tolerance by the lupus susceptibility gene Ly108
Kirthi Raman Kumar et al. Science. 2006.
Abstract
The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.
Comment in
- Immunology. Discriminating microbe from self suffers a double toll.
Goodnow CC. Goodnow CC. Science. 2006 Jun 16;312(5780):1606-8. doi: 10.1126/science.1129797. Science. 2006. PMID: 16778043 No abstract available.
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