Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor

Catherine M. Radcliffe, James N. Arnold, David M. Suter, Mark R. Wormald, David J. Harvey, Louise Royle, Yusuke Mimura, Yoshinobu Kimura, Robert B. Sim, Susana Inogès, Mercedes Rodriguez-Calvillo, Natalia Zabalegui, Ascension Lopez Diaz De Cerio, Kathleen N. Potter, C. Ian Mockridge, Raymond A. Dwek, Maurizio Bendandi, Pauline M. Rudd, Freda K. Stevenson

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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.

Original languageEnglish
Pages (from-to)7405-7415
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number10
DOIs
Publication statusPublished - Mar 2 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Radcliffe, C. M., Arnold, J. N., Suter, D. M., Wormald, M. R., Harvey, D. J., Royle, L., Mimura, Y., Kimura, Y., Sim, R. B., Inogès, S., Rodriguez-Calvillo, M., Zabalegui, N., De Cerio, A. L. D., Potter, K. N., Mockridge, C. I., Dwek, R. A., Bendandi, M., Rudd, P. M., & Stevenson, F. 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. https://doi.org/10.1074/jbc.M602690200