title: Copresentation of antigen and ligands of Siglec-G induces B cell tolerance independent of CD22.
abstract: Differentiation of self from nonself is indispensable for maintaining B cell tolerance in peripheral tissues. CD22 and Siglec-G (sialic acid-binding Ig-like lectin G) are two inhibitory coreceptors of the BCR that are implicated in maintenance of tolerance to self Ags. Enforced ligation of CD22 and the BCR by a nanoparticle displaying both Ag and CD22 ligands induces a tolerogenic circuit resulting in apoptosis of the Ag-reactive B cell. Whether Siglec-G also has this property has not been investigated in large part owing to the lack of a selective Siglec-G ligand. In this article, we report the development of a selective high-affinity ligand for Siglec-G and its application as a chemical tool to investigate the tolerogenic potential of Siglec-G. We find that liposomal nanoparticles decorated with Ag and Siglec-G ligand inhibit BCR signaling in both B1 and B2 B cells compared with liposomes displaying Ag alone. Not only is inhibition of B cell activation observed by ligating the BCR with Siglec-G, but robust tolerance toward T-independent and T-dependent Ags is also induced in mice. The ability of Siglec-G to inhibit B cell activation equally in both B1 and B2 subsets is consistent with our observation that Siglec-G is expressed at a relatively constant level throughout numerous B cell subsets. These results suggest that Siglec-G may contribute to maintenance of B cell tolerance toward self Ags in various B cell compartments.
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Pfrengle
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Macauley
authors.forename: Norihito
authors.initials: N
authors.lastname: Kawasaki
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D020013:Calcium Signaling; D003713:Dendritic Cells / Q000276:immunology; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology; D007108:Immune Tolerance / Q000276:immunology*; D007156:Immunologic Memory; D037102:Lectins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D008081:Liposomes; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009928:Organ Specificity; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D000911:Antibodies, Monoclonal; C497868:Cd22 protein, mouse; D037102:Lectins; D008024:Ligands; D008081:Liposomes; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse