title: Germinal center marker GL7 probes activation-dependent repression of N-glycolylneuraminic acid, a sialic acid species involved in the negative modulation of B-cell activation.
abstract: Sialic acid (Sia) is a family of acidic nine-carbon sugars that occupies the nonreducing terminus of glycan chains. Diversity of Sia is achieved by variation in the linkage to the underlying sugar and modification of the Sia molecule. Here we identified Sia-dependent epitope specificity for GL7, a rat monoclonal antibody, to probe germinal centers upon T cell-dependent immunity. GL7 recognizes sialylated glycan(s), the alpha2,6-linked N-acetylneuraminic acid (Neu5Ac) on a lactosamine glycan chain(s), in both Sia modification- and Sia linkage-dependent manners. In mouse germinal center B cells, the expression of the GL7 epitope was upregulated due to the in situ repression of CMP-Neu5Ac hydroxylase (Cmah), the enzyme responsible for Sia modification of Neu5Ac to Neu5Gc. Such Cmah repression caused activation-dependent dynamic reduction of CD22 ligand expression without losing alpha2,6-linked sialylation in germinal centers. The in vivo function of Cmah was analyzed using gene-disrupted mice. Phenotypic analyses showed that Neu5Gc glycan functions as a negative regulator for B-cell activation in assays of T-cell-independent immunization response and splenic B-cell proliferation. Thus, Neu5Gc is required for optimal negative regulation, and the reaction is specifically suppressed in activated B cells, i.e., germinal center B cells.
authors.affiliation: Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida-shimoadachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Naito
authors.forename: Hiromu
authors.initials: H
authors.lastname: Takematsu
authors.forename: Susumu
authors.initials: S
authors.lastname: Koyama
authors.forename: Shizu
authors.initials: S
authors.lastname: Miyake
authors.forename: Harumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Reiko
authors.initials: R
authors.lastname: Fujinawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Sugai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okuno
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamaji
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Akemi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kozutsumi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D000939:Epitopes / Q000276:immunology; D018390:Gene Targeting; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D006899:Mixed Function Oxygenases / Q000172:deficiency / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009438:Neuraminic Acids / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D012799:Sialyltransferases / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D037102:Lectins; D008024:Ligands; D009438:Neuraminic Acids; D011134:Polysaccharides; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C032592:N-glycolylneuraminic acid; D019000:Phosphotyrosine; D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase