TY - JOUR
T1 - Regulation of B cell tolerance by the lupus susceptibility gene Ly108
AU - Kumar, Kirthi Raman
AU - Li, Liunan
AU - Yan, Mei
AU - Bhaskarabhatla, Madhavi
AU - Mobley, Angela B.
AU - Nguyen, Charles
AU - Mooney, Jill M.
AU - Schatzle, John D.
AU - Wakeland, Edward K.
AU - Mohan, Chandra
PY - 2006/6/16
Y1 - 2006/6/16
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1125893
DO - 10.1126/science.1125893
M3 - Article
C2 - 16778059
AN - SCOPUS:33745161013
SN - 0036-8075
VL - 312
SP - 1665
EP - 1669
JO - Science
JF - Science
IS - 5780
ER -