title: Siglec-G/10 in self-nonself discrimination of innate and adaptive immunity.
abstract: Siglec-G/10 is broadly expressed on B cells, dendritic cells and macrophage subsets. It binds strongly to CD24, a small glycosyl-phosphatidylinositol-anchored sialoprotein, in a sialylation-dependent manner. Targeted mutation of Siglecg dramatically elevates the level of natural IgM antibodies and its producer, B1 B cells. Incorporation of Siglec-G ligands to both T-dependent and T-independent immunogens reduces antibody production and induces B-cell tolerance to subsequent antigen challenges. By interacting with CD24, Siglec-G suppresses inflammatory responses to danger (damage)-associated molecular patterns, such as heat-shock proteins and high mobility group protein 1, but not to Toll-like receptor ligands. By a CD24-independent mechanism, Siglec-G has been shown to associate with Cbl to cause degradation of retinoic acid-inducible gene 1 and reduce production of type I interferon in response to RNA virus infection. The negative regulation by Siglec-G/10 may provide a mechanism for the host to discriminate between infectious nonself and noninfectious self, as envisioned by the late Dr. Charles A. Janeway.
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA Department of Pediatrics, School of Medicine and Health Sciences, George Washington University gchen@cnmc.org yaliu@cnmc.org.
authors.forename: Guo-Yun
authors.initials: GY
authors.lastname: Chen
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Brown
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA Division of Pathology, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA gchen@cnmc.org yaliu@cnmc.org.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism
chemical_list: D051927:CD24 Antigen; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D012794:Sialic Acids
keywords: DAMP; PAMP; Siglec-G; self–nonself