title: Siglec-G Deficiency Leads to Autoimmunity in Aging C57BL/6 Mice.
abstract: Siglec-G, a member of the sialic acid-binding Ig-like lectin (Siglec) family, is expressed on B cell and dendritic cell surfaces. It acts as an inhibitory coreceptor and modulates B cell activation, especially on B1 cells, as Siglec-G-deficient mice show mainly a B1 cell-restricted phenotype resulting in increased B1 cell numbers. Although higher B1 cell numbers are discussed to be associated with autoimmunity, loss of Siglec-G does not result in autoimmune disease in BALB/c mice. However, there is evidence from Siglec-G × CD22 double-deficient mice and Siglec-G(-/-) mice on an autoimmune-prone MRL/lpr background that Siglec-G is important to maintain tolerance in B cells. In this study, we analyzed the role of Siglec-G in induction and maintenance of B cell tolerance on C57BL/6 background and in the FcγRIIb-deficient background. We find that aging Siglec-G-deficient and Siglec-G × FcγRIIb double-deficient mice develop an autoimmune phenotype with elevated autoantibody levels and mild glomerulonephritis. Aging Siglec-G-deficient mice have elevated numbers of plasma cells and germinal center B cells, as well as a higher number of activated CD4 T cells, which likely all contribute to autoantibody production. Additional loss of the inhibitory receptor FcγRIIb in Siglec-G(-/-) mice does not result in exacerbation of disease. These results indicate that Siglec-G is important to maintain tolerance in B cells and prevent autoimmunity.
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Müller
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany; and.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lunz
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany; and.
authors.forename: Inessa
authors.initials: I
authors.lastname: Schwab
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany; and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Acs
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany; and.
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.affiliation: Department of Nephropathology, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany; and lars.nitschke@fau.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003433:Crosses, Genetic; D005260:Female; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance; D037102:Lectins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D001323:Autoantibodies; C499172:Fcgr2b protein, mouse; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse