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Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins

Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins
Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins
Surface Ig (sIg) of follicular lymphoma (FL) is vital for tumor cell survival. We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for N-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of FL cells with mannose-binding lectins of the innate immune system. We have now identified mannosylated IgM at the surface of primary lymphoma cells. Recombinant lectin domains of the mannose receptor (MR) or DC-SIGN bind mannosylated Igs in vitro and bind to FL cells, signaling sIgM-associated increases in intracellular Ca(2+). Lectins also bind to normal B cells but fail to signal. In contrast, anti-Ig signaled similarly in both FL and normal B cells. Mannosylation patterns were mimicked by FL Ig-derived single-chain Fvs (scFv), providing probes for potential receptors. Mannosylated scFv bound specifically to the lectin domains of the MR and DC-SIGN and blocked signaling. Mannosylated scFv also bound to DC-SIGN on the surface of dendritic cells. This unique lymphoma-specific interaction of sIg with lectins of innate immunity reveals a potential route for microenvironmental support of tumor cells, mediated via the key B-cell receptor.
b cell, b-cell receptor, b-cell lymphoma, immunoglobulin
0027-8424
18587-18592
Coelho, Vania
f037a720-66df-49fd-880a-9015155f72c4
Krysov, Sergey
3a78eac1-af40-4b37-8576-3462947649be
Ghaemmaghami, Amir M.
2d0f8977-c0eb-4c20-8e0d-1e93b25589ee
Emara, Mohamed
5e14a804-61a6-463b-ac7f-0c7c6a87e7dd
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Martinez-Pomares, Luisa
5e28882e-a677-423c-ac59-e902ab49bf0f
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Coelho, Vania
f037a720-66df-49fd-880a-9015155f72c4
Krysov, Sergey
3a78eac1-af40-4b37-8576-3462947649be
Ghaemmaghami, Amir M.
2d0f8977-c0eb-4c20-8e0d-1e93b25589ee
Emara, Mohamed
5e14a804-61a6-463b-ac7f-0c7c6a87e7dd
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Martinez-Pomares, Luisa
5e28882e-a677-423c-ac59-e902ab49bf0f
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Coelho, Vania, Krysov, Sergey, Ghaemmaghami, Amir M., Emara, Mohamed, Potter, Kathleen N., Johnson, Peter, Packham, Graham, Martinez-Pomares, Luisa and Stevenson, Freda K. (2010) Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins. Proceedings of the National Academy of Sciences of the United States of America, 107 (43), 18587-18592. (doi:10.1073/pnas.1009388107). (PMID:20937880)

Record type: Article

Abstract

Surface Ig (sIg) of follicular lymphoma (FL) is vital for tumor cell survival. We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for N-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of FL cells with mannose-binding lectins of the innate immune system. We have now identified mannosylated IgM at the surface of primary lymphoma cells. Recombinant lectin domains of the mannose receptor (MR) or DC-SIGN bind mannosylated Igs in vitro and bind to FL cells, signaling sIgM-associated increases in intracellular Ca(2+). Lectins also bind to normal B cells but fail to signal. In contrast, anti-Ig signaled similarly in both FL and normal B cells. Mannosylation patterns were mimicked by FL Ig-derived single-chain Fvs (scFv), providing probes for potential receptors. Mannosylated scFv bound specifically to the lectin domains of the MR and DC-SIGN and blocked signaling. Mannosylated scFv also bound to DC-SIGN on the surface of dendritic cells. This unique lymphoma-specific interaction of sIg with lectins of innate immunity reveals a potential route for microenvironmental support of tumor cells, mediated via the key B-cell receptor.

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More information

Published date: 26 October 2010
Keywords: b cell, b-cell receptor, b-cell lymphoma, immunoglobulin
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 179123
URI: http://eprints.soton.ac.uk/id/eprint/179123
ISSN: 0027-8424
PURE UUID: d72dec8b-116e-444b-9274-9f941fa2732c
ORCID for Peter Johnson: ORCID iD orcid.org/0000-0003-2306-4974
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 31 Mar 2011 11:33
Last modified: 15 Mar 2024 03:05

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Contributors

Author: Vania Coelho
Author: Sergey Krysov
Author: Amir M. Ghaemmaghami
Author: Mohamed Emara
Author: Peter Johnson ORCID iD
Author: Graham Packham ORCID iD
Author: Luisa Martinez-Pomares

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