Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor
Radcliffe, Catherine M., Arnold, James N., Suter, David M., Wormald, Mark R., Harvey, David J., Royle, Louise, Mimura, Yusuke, Kimura, Yoshinobu, Sim, Robert B., Inogès, Susana, Rodriguez-Calvillo, Mercedes, Zabalegui, Natalia, de Cerio, Ascensión López-Díaz, Potter, Kathleeen N., Mockridge, C. Ian, Dwek, Raymond A., Bendandi, Maurizio, Rudd, Pauline M. and Stevenson, Freda K. (2007) Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor. Journal of Biological Chemistry, 282, (10), 7405-7415. (doi:10.1074/jbc.M602690200).
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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.
|Keywords:||variable region, indicate, surface, pathogenesis, receptor, surface-immunoglobulin, molecules, survival, c-type lectins, follicular lymphoma, dendritic cells,antigen, time, b-cell receptor, mutation, expression, region, involvement, lymphoma, burkitts-lymphoma, pathway, tumor, b-cell lymphoma, rheumatoid-arthritis, growth, fab fragment, immune-system, glycosylation sites, somatic mutation, binding, n-linked oligosaccharides, immunity, cells, innate, cell, immunoglobulin, b cell, b-cell-receptor, sites|
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QR Microbiology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||12 Sep 2008|
|Last Modified:||27 Mar 2014 18:44|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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