Deficiency in activation-induced cytidine deaminase promotes systemic autoimmunity in lpr mice on a C57BL/6 background.

Clinical and Experimental Immunology
L ChenS Han

Abstract

Activation-induced deaminase (AID) is a prerequisite for immunoglobulin (Ig) class-switch recombination and somatic hypermutation, which is critical for antibody affinity maturation. IgM and IgG autoantibodies are characteristic of the systemic autoimmune disorders such as lupus. However, the relative contributions of hypermutated high-affinity IgG antibodies and germline-encoded IgM antibodies to systemic autoimmunity are not defined fully. The role of AID in autoimmunity is unclear. The current study used AID-deficient mice to investigate the role of AID in the development and pathogenesis of murine lupus. C57BL/6 mice deficient in both Fas and AID were generated. Compared to their AID-competent littermates, AID(-/-) lymphoproliferative (lpr) mice produced significantly elevated levels of IgM autoreactive antibodies with enhanced germinal centre (GC) response, developed more advanced splenomegaly and exhibited more severe glomerulonephritis. Thus, AID may play an important role in the negative regulation of systemic autoimmune manifestations in murine lupus. The results also indicate that hypermutated high-affinity IgG antibodies are not necessary for the development of autoimmune syndrome in lpr mice on a C57BL/6 background.

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Citations

Jun 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Masayuki KuraokaGarnett Kelsoe
Jun 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Greta MeyersEric Meffre
Feb 9, 2011·The Journal of Experimental Medicine·Taku OkazakiTasuku Honjo
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Jan 28, 2019·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Parisa AmirifarAsghar Aghamohammadi
Mar 3, 2020·Immunological Investigations·Parisa AmirifarAsghar Aghamohammadi
Jan 29, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jing ZhuCaroline M Leeth
Feb 7, 2017·Expert Review of Clinical Immunology·Saleh GhiasyAsghar Aghamohammadi
Feb 7, 2021·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Parisa AmirifarHassan Abolhassani
Oct 11, 2021·Journal of Clinical Immunology·Parisa AmirifarAsghar Aghamohammadi

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