title: CD22 and Siglec-G regulate inhibition of B-cell signaling by sialic acid ligand binding and control B-cell tolerance.
abstract: CD22 and Siglec-G are two B-cell expressed members of the Siglec (sialic acid-binding immunoglobulin (Ig)-like lectin) family and are potent inhibitors of B-cell signaling. Genetic approaches have provided evidence that this inhibition of B-cell antigen receptor (BCR) signaling by Siglecs is dependent on ligand binding to sialic acids in specific linkages. The cis-ligand-binding activity of CD22 leads to homo-oligomer formation, which are to a large extent found in membrane domains that are distinct from those containing the BCR. In contrast, Siglec-G is recruited via sialic acid binding to the BCR. This interaction of Siglec-G with mIgM leads to an inhibitory function that seems to be specific for B-1 cells. Both CD22 and Siglec-G control B-cell tolerance and loss of these proteins, its ligands or its inhibitory pathways can increase the susceptibility for autoimmune diseases. CD22 is a target protein both in B-cell leukemias and lymphomas, as well as in B-cell mediated autoimmune diseases. Both antibodies and synthetic chemically modified sialic acids are currently tested to target Siglecs on B cells.
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany lars.nitschke@fau.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D037102:Lectins / Q000276:immunology / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology / Q000378:metabolism*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D015398:Signal Transduction
chemical_list: D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D019158:N-Acetylneuraminic Acid
keywords: B lymphocytes; Siglecs; autoimmunity; inhibitory signaling