Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor.
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.
Radcliffe
Catherine M
CM
Glycobiology Institute, Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Arnold
James N
JN
Suter
David M
DM
Wormald
Mark R
MR
Harvey
David J
DJ
Royle
Louise
L
Mimura
Yusuke
Y
Kimura
Yoshinobu
Y
Sim
Robert B
RB
Inogès
Susana
S
Rodriguez-Calvillo
Mercedes
M
Zabalegui
Natalia
N
de Cerio
Ascensión López-Díaz
AL
Potter
Kathleen N
KN
Mockridge
C Ian
CI
Dwek
Raymond A
RA
Bendandi
Maurizio
M
Rudd
Pauline M
PM
Stevenson
Freda K
FK
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
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