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Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma

Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma
Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma
Most patients with follicular lymphoma (FL) have somatically mutated V genes with intraclonal variation, consistent with location in the germinal center site. Using our own and published sequences, we have investigated the frequency of potential N-glycosylation sites introduced into functional VH genes as a consequence of somatic mutation. FL cells were compared with normal memory B cells or plasma cells matched for similar levels of mutation. Strikingly, novel sites were detected in 55 of 70 (79%) patients with FL, compared to 7 of 75 (9%) in the normal B-cell population (P < .001). Diffuse large B-cell lymphoma (DLCL) showed an intermediate frequency (13 of 32 [41%] patients). Myeloma and the mutated subset of chronic lymphocytic leukemia showed frequencies similar to those of normal cells in 5 of 64 (8%) patients and 5 of 40 (13%) patients, respectively. In 3 of 3 random patients with FL, immunoglobulin was expressed as recombinant single-chain Fv in Pichia pastoris, and glycosylation was demonstrated. These findings indicate that N-glycosylation of the variable region may be common in FL and in a subset of DLCL. Most novel sites are located in the complementarity-determining regions. VH sequences of nonfunctional VH genes contained few sites, arguing for positive selection in FL. One possibility is that the added carbohydrate in the variable region contributes to interaction with elements in the germinal center environment. This common feature of FL may be critical for tumor behavior.
0006-4971
2562-2568
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5
McCarthy, Helen
26fef320-0597-4a97-b054-f2ae8e8a50d7
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Hamblin, Terry J.
57389613-7900-48fd-b3e6-8ca8fbdceccb
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5
McCarthy, Helen
26fef320-0597-4a97-b054-f2ae8e8a50d7
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Hamblin, Terry J.
57389613-7900-48fd-b3e6-8ca8fbdceccb
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Zhu, Delin, McCarthy, Helen, Ottensmeier, Christian H., Johnson, Peter, Hamblin, Terry J. and Stevenson, Freda K. (2002) Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma. Blood, 99 (7), 2562-2568. (doi:10.1182/blood.V99.7.2562).

Record type: Article

Abstract

Most patients with follicular lymphoma (FL) have somatically mutated V genes with intraclonal variation, consistent with location in the germinal center site. Using our own and published sequences, we have investigated the frequency of potential N-glycosylation sites introduced into functional VH genes as a consequence of somatic mutation. FL cells were compared with normal memory B cells or plasma cells matched for similar levels of mutation. Strikingly, novel sites were detected in 55 of 70 (79%) patients with FL, compared to 7 of 75 (9%) in the normal B-cell population (P < .001). Diffuse large B-cell lymphoma (DLCL) showed an intermediate frequency (13 of 32 [41%] patients). Myeloma and the mutated subset of chronic lymphocytic leukemia showed frequencies similar to those of normal cells in 5 of 64 (8%) patients and 5 of 40 (13%) patients, respectively. In 3 of 3 random patients with FL, immunoglobulin was expressed as recombinant single-chain Fv in Pichia pastoris, and glycosylation was demonstrated. These findings indicate that N-glycosylation of the variable region may be common in FL and in a subset of DLCL. Most novel sites are located in the complementarity-determining regions. VH sequences of nonfunctional VH genes contained few sites, arguing for positive selection in FL. One possibility is that the added carbohydrate in the variable region contributes to interaction with elements in the germinal center environment. This common feature of FL may be critical for tumor behavior.

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Published date: 1 April 2002

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Local EPrints ID: 26677
URI: http://eprints.soton.ac.uk/id/eprint/26677
ISSN: 0006-4971
PURE UUID: 0b8c7635-2659-4b30-9dd4-7d5f2e3beaf1
ORCID for Peter Johnson: ORCID iD orcid.org/0000-0003-2306-4974
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 24 Apr 2006
Last modified: 10 Dec 2019 01:53

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Author: Delin Zhu
Author: Helen McCarthy
Author: Peter Johnson ORCID iD
Author: Terry J. Hamblin

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