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

BMC Immunology

Toshiyuki Takai²  Sachiko Hirose¹  Akira Nakamura³  Masanori Inui²  Haruka Takahashi²  Akiko Sugahara–Tobinai²  Yasuyoshi Kanari² 

[1] Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku 113-8421, Tokyo, Japan;Department of Experimental Immunology and CREST Program of JST, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan;Department of Immunology, Kanazawa Medical University, Kanazawa 920-0293, Ishikawa, Japan

关键词: Inhibitory receptor;    Myeloid cells;    B cells;    Autoantibody production;    Systemic lupus erythematosus;    Autoimmune disease;   

Others  :  1077687
DOI  :  10.1186/s12865-014-0047-y

 received in 2014-06-28, accepted in 2014-10-09,  发布年份 2014

【 摘 要 】

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.

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.

【 授权许可】

   
2014 Kanari et al.; licensee BioMed Central Ltd.

【 图 表 】

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