Immune Netw.  2019 Feb;19(1):e1. 10.4110/in.2019.19.e1.

CD72 is a Negative Regulator of B Cell Responses to Nuclear Lupus Self-antigens and Development of Systemic Lupus Erythematosus

Affiliations
  • 1Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. tsubata.imm@mri.tmd.ac.jp

Abstract

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of anti-microbial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72−/− mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.

Keyword

Systemic lupus erythematosus; CD72; Inhibitory B cell co-receptor; Sm/RNP; NA sensors; Autoimmunity

MeSH Terms

Animals
Antigens, Nuclear
Autoantibodies
Autoantigens*
Autoimmune Diseases
Autoimmunity
B-Lymphocytes
Cytoplasm
Dendritic Cells
Discrimination (Psychology)
Humans
Immunoreceptor Tyrosine-Based Inhibition Motif
Lectins, C-Type
Lupus Erythematosus, Systemic*
Mice
RNA
Antigens, Nuclear
Autoantibodies
Autoantigens
Lectins, C-Type
RNA
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