Dichotomy in FcγRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis

Yasuyoshi Kanari, Akiko Sugahara-Tobinai, Haruka Takahashi, Masanori Inui, Akira Nakamura, Sachiko Hirose, Toshiyuki Takai

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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 locus is adjacent to the autoimmune-related locus harboring the genes coding for signaling lymphocyte activation molecules, making it difficult to isolate the effect of RIIB deletion from that of in gene-targeted mice. Our objective was to determine the influence of deletion on the spontaneous development of autoimmune diseases and to compare it with that of potentially pathogenic . Results: We established two congenic C57BL/6 (B6) strains, one with the deletion and the other with , by backcrossing 129/SvJ-based -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 in the B6 genetic background induced ANAs but no IgG immune-complex deposition in the kidneys. Naïve mice but not RIIB-deficient mice exhibited hyperplasia of splenic germinal centers. Conclusion: 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.

Original languageEnglish
Article number47
JournalBMC immunology
Volume15
Issue number1
DOIs
Publication statusPublished - 2014 Oct 24

Keywords

  • Autoantibody production
  • Autoimmune disease
  • B cells
  • Inhibitory receptor
  • Myeloid cells
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology

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