title: Regulation of B cell tolerance by the lupus susceptibility gene Ly108.
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.
authors.affiliation: Department of Internal Medicine (Rheumatology), University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kirthi Raman
authors.initials: KR
authors.lastname: Kumar
authors.forename: Liunan
authors.initials: L
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.forename: Madhavi
authors.initials: M
authors.lastname: Bhaskarabhatla
authors.forename: Angela B
authors.initials: AB
authors.lastname: Mobley
authors.forename: Charles
authors.initials: C
authors.lastname: Nguyen
authors.forename: Jill M
authors.initials: JM
authors.lastname: Mooney
authors.forename: John D
authors.initials: JD
authors.lastname: Schatzle
authors.forename: Edward K
authors.initials: EK
authors.lastname: Wakeland
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D016923:Cell Death; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017635:Clonal Anergy; D017637:Clonal Deletion; D020022:Genetic Predisposition to Disease; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020412:Multifactorial Inheritance; D009113:Muramidase / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014162:Transfection; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D000950:Antigens, Ly; D001324:Autoantigens; D009113:Muramidase; D011947:Receptors, Antigen, B-Cell; C421864:hen egg lysozyme; C000604063:Slamf6 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family