title: Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor.
abstract: Expression of surface immunoglobulin appears critical for the growth and survival of B-cell lymphomas. In follicular lymphoma, we found previously that the Ig variable (V) regions in the B-cell receptor express a strikingly high incidence of N-glycosylation sequons, NX(S/T). These potential glycosylation sites are introduced by somatic mutation and are lymphoma-specific, pointing to their involvement in tumor pathogenesis. Analysis of the V region sugars from lymphoma-derived IgG/IgM reveals that they are mostly oligomannose and, remarkably, are located in the antigen-binding site, possibly precluding conventional antigen binding. The Fc region contains complex glycans, confirming that the normal glycan processing pathway is intact. Binding studies indicate that the oligomannose glycans occupying the V regions are accessible to mannose-binding lectin. These findings suggest a potential contribution to lymphoma pathogenesis involving antigen-independent interaction of surface immunoglobulin of the B-cell receptor with mannose-binding molecules of innate immunity in the germinal center.
authors.affiliation: Glycobiology Institute, Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Radcliffe
authors.forename: James N
authors.initials: JN
authors.lastname: Arnold
authors.forename: David M
authors.initials: DM
authors.lastname: Suter
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wormald
authors.forename: David J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Louise
authors.initials: L
authors.lastname: Royle
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mimura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kimura
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Susana
authors.initials: S
authors.lastname: Inogès
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rodriguez-Calvillo
authors.forename: Natalia
authors.initials: N
authors.lastname: Zabalegui
authors.forename: Ascensión López-Díaz
authors.initials: AL
authors.lastname: de Cerio
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Potter
authors.forename: C Ian
authors.initials: CI
authors.lastname: Mockridge
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dwek
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bendandi
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
mesh_terms: D001665:Binding Sites; D006031:Glycosylation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D037181:Lectins, C-Type / Q000502:physiology; D008224:Lymphoma, Follicular / Q000209:etiology / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000378:metabolism; D008958:Models, Molecular; D009844:Oligosaccharides / Q000032:analysis* / Q000502:physiology; D010206:Papain / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000737:chemistry*; D043323:alpha-Mannosidase / Q000378:metabolism
chemical_list: D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D037181:Lectins, C-Type; D037601:Mannose-Binding Lectin; D009844:Oligosaccharides; D011947:Receptors, Antigen, B-Cell; C028569:oligomannoside; D043323:alpha-Mannosidase; D010206:Papain