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Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma

Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma
Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma
B-cell antigen receptor (BCR) expression is a key feature of most B-cell lymphomas, but the mechanisms of BCR signal induction and the involvement of autoantigen recognition remain unclear. In follicular lymphoma (FL) B cells, BCR expression is retained despite a chromosomal translocation that links the antiapoptotic gene BCL2 to the regulatory elements of immunoglobulin genes, thereby disrupting 1 heavy-chain allele. A remarkable feature of FL-BCRs is the acquisition of potential N-glycosylation sites during somatic hypermutation. The introduced glycans carry mannose termini, which create potential novel binding sites for mannose-specific lectins. Here, we investigated the effect of N-linked variable-region glycosylation for BCR interaction with cognate antigen and with lectins of different origins. N-glycans were found to severely impair BCR specificity and affinity to the initial cognate antigen. In addition, we found that lectins from Pseudomonas aeruginosa and Burkholderia cenocepacia bind and stimulate FL cells. Human exposure to these bacteria can occur by contact with soil and water. In addition, they represent opportunistic pathogens in susceptible hosts. Understanding the role of bacterial lectins might elucidate the pathogenesis of FL and establish novel therapeutic approaches.
0006-4971
3287-3296
Schneider, Dunja
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Dühren-von Minden, Marcus
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Alkhatib, Alabbas
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Setz, Corinna
d478e297-e913-4179-911e-d15f64f7d880
van Bergen, Cornelis A.M.
ff876d52-76ee-4325-8e06-30edcf6b4c25
Benkißer-Petersen, Marco
a4fc4e4c-c3b2-4b64-91a7-ed095c82b4f1
Wilhelm, Isabel
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Villringer, Sarah
e8d40c2b-83a1-4732-82f1-34256d09dde3
Krysov, Sergey
717c5d0a-ee60-4760-8adc-b4662e27e09b
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Zirlik, Katja
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Römer, Winfried
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Buske, Christian
318e2827-0566-4bc8-9edb-07bf12df704f
Stevenson, Freda K.
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Veelken, Hendrik
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Jumaa, Hassan
263896a4-ace6-4bc8-b521-9153594d24f3
Schneider, Dunja
40dcbd22-d514-4656-9016-5a9cb90e4323
Dühren-von Minden, Marcus
2ae38b12-50c1-4df6-b49a-493f0c5bb403
Alkhatib, Alabbas
e4da1111-f3c3-4dd9-a1ff-2cfdee045e2b
Setz, Corinna
d478e297-e913-4179-911e-d15f64f7d880
van Bergen, Cornelis A.M.
ff876d52-76ee-4325-8e06-30edcf6b4c25
Benkißer-Petersen, Marco
a4fc4e4c-c3b2-4b64-91a7-ed095c82b4f1
Wilhelm, Isabel
f8a65ff3-925f-4bcd-aecb-f7ce327935ca
Villringer, Sarah
e8d40c2b-83a1-4732-82f1-34256d09dde3
Krysov, Sergey
717c5d0a-ee60-4760-8adc-b4662e27e09b
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Zirlik, Katja
fac736c7-b166-4a10-ae6d-6861322cd91a
Römer, Winfried
eb8e7735-664b-430b-bd96-68cdb3290842
Buske, Christian
318e2827-0566-4bc8-9edb-07bf12df704f
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Veelken, Hendrik
e77cf6ab-7e07-4ab3-912e-bc1e1c624571
Jumaa, Hassan
263896a4-ace6-4bc8-b521-9153594d24f3

Schneider, Dunja, Dühren-von Minden, Marcus, Alkhatib, Alabbas, Setz, Corinna, van Bergen, Cornelis A.M., Benkißer-Petersen, Marco, Wilhelm, Isabel, Villringer, Sarah, Krysov, Sergey, Packham, Graham, Zirlik, Katja, Römer, Winfried, Buske, Christian, Stevenson, Freda K., Veelken, Hendrik and Jumaa, Hassan (2015) Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma. Blood, 125 (21), 3287-3296. (doi:10.1182/blood-2014-11-609404). (PMID:25784678)

Record type: Article

Abstract

B-cell antigen receptor (BCR) expression is a key feature of most B-cell lymphomas, but the mechanisms of BCR signal induction and the involvement of autoantigen recognition remain unclear. In follicular lymphoma (FL) B cells, BCR expression is retained despite a chromosomal translocation that links the antiapoptotic gene BCL2 to the regulatory elements of immunoglobulin genes, thereby disrupting 1 heavy-chain allele. A remarkable feature of FL-BCRs is the acquisition of potential N-glycosylation sites during somatic hypermutation. The introduced glycans carry mannose termini, which create potential novel binding sites for mannose-specific lectins. Here, we investigated the effect of N-linked variable-region glycosylation for BCR interaction with cognate antigen and with lectins of different origins. N-glycans were found to severely impair BCR specificity and affinity to the initial cognate antigen. In addition, we found that lectins from Pseudomonas aeruginosa and Burkholderia cenocepacia bind and stimulate FL cells. Human exposure to these bacteria can occur by contact with soil and water. In addition, they represent opportunistic pathogens in susceptible hosts. Understanding the role of bacterial lectins might elucidate the pathogenesis of FL and establish novel therapeutic approaches.

Text
MS BLOOD-2015-660969 Yeomans et al manuscript version 2.pdf - Accepted Manuscript
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More information

Accepted/In Press date: 10 March 2015
e-pub ahead of print date: 17 March 2015
Published date: 21 May 2015
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 385499
URI: http://eprints.soton.ac.uk/id/eprint/385499
ISSN: 0006-4971
PURE UUID: b40908bd-58f7-4f92-a065-383134276e1b
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: 20 Jan 2016 11:43
Last modified: 15 Mar 2024 03:05

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Contributors

Author: Dunja Schneider
Author: Marcus Dühren-von Minden
Author: Alabbas Alkhatib
Author: Corinna Setz
Author: Cornelis A.M. van Bergen
Author: Marco Benkißer-Petersen
Author: Isabel Wilhelm
Author: Sarah Villringer
Author: Sergey Krysov
Author: Graham Packham ORCID iD
Author: Katja Zirlik
Author: Winfried Römer
Author: Christian Buske
Author: Hendrik Veelken
Author: Hassan Jumaa

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