title: Dichotomy in FcγRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis.
abstract: BACKGROUND
  The significance of a unique inhibitory Fc receptor for IgG, FcγRIIB (RIIB), in the prevention of spontaneous production of autoantibodies remains controversial, due mainly to the fact that the RIIB locus is adjacent to the autoimmune-related SLAM locus harboring the genes coding for signaling lymphocyte activation molecules, making it difficult to isolate the effect of RIIB deletion from that of SLAM in gene-targeted mice. Our objective was to determine the influence of RIIB deletion on the spontaneous development of autoimmune diseases and to compare it with that of potentially pathogenic SLAM.
  
  
  RESULTS
  We established two congenic C57BL/6 (B6) strains, one with the RIIB deletion and the other with SLAM, by backcrossing 129/SvJ-based RIIB-deficient mice into the B6 genetic background extensively. The RIIB deficiency indeed led to the production and/or accumulation of a small amount of anti-nuclear autoantibodies (ANAs) and to weak IgG immune-complex deposition in glomeruli without any obvious manifestation of lupus nephritis. In contrast, pathogenic SLAM in the B6 genetic background induced ANAs but no IgG immune-complex deposition in the kidneys. Naïve SLAM mice but not RIIB-deficient mice exhibited hyperplasia of splenic germinal centers.
  
  
  CONCLUSIONS
  The present results clarify the roles of RIIB in preventing production and/or accumulation of a small amount of ANAs, and development of glomerulonephritis. The combined effects of RIIB deletion and pathogenic SLAM can lead to severe lupus nephritis in the B6 genetic background.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Kanari
authors.forename: Akiko
authors.initials: A
authors.lastname: Sugahara-Tobinai
authors.forename: Haruka
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Inui
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Department of Experimental Immunology and CREST Program of JST, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan. tostakai@idac.tohoku.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D033481:Chromosomes, Mammalian / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D018858:Germinal Center / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology*; D006239:Haplotypes / Q000235:genetics*; D018655:Lymphocyte Count; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000378:metabolism*; D017452:Receptors, IgG / Q000172:deficiency* / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013154:Spleen / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D001323:Autoantibodies; C080571:Fc gamma receptor IIB; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1