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Blood. 2015 May 21;125(21):3287-96. doi: 10.1182/blood-2014-11-609404. Epub 2015 Mar 17.

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

Author information

1
Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg and Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany;
2
Institute of Immunology, Ulm University Medical Center, Ulm, Germany;
3
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands;
4
Department of Hematology/Oncology, University Medical Center Freiburg, Freiburg, Germany;
5
Centre for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany; Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs University of Freiburg, Freiburg, Germany;
6
Centre for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany; Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany;
7
Molecular Immunology Group, Cancer Sciences Unit, Cancer Research UK Centre, University of Southampton Faculty of Medicine, Southampton, United Kingdom; and.
8
Institute for Experimental Cancer Research, Comprehensive Cancer Center Ulm, Ulm, Germany.
9
Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg and Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany; Institute of Immunology, Ulm University Medical Center, Ulm, Germany;

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.

PMID:
25784678
PMCID:
PMC4482265
DOI:
10.1182/blood-2014-11-609404
[Indexed for MEDLINE]
Free PMC Article

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