title: Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma.
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.
authors.affiliation: Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg and Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany;
authors.forename: Dunja
authors.initials: D
authors.lastname: Schneider
authors.affiliation: Institute of Immunology, Ulm University Medical Center, Ulm, Germany;
authors.forename: Marcus
authors.initials: M
authors.lastname: Dühren-von Minden
authors.affiliation: Institute of Immunology, Ulm University Medical Center, Ulm, Germany;
authors.forename: Alabbas
authors.initials: A
authors.lastname: Alkhatib
authors.affiliation: Institute of Immunology, Ulm University Medical Center, Ulm, Germany;
authors.forename: Corinna
authors.initials: C
authors.lastname: Setz
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: van Bergen
authors.affiliation: Department of Hematology/Oncology, University Medical Center Freiburg, Freiburg, Germany;
authors.forename: Marco
authors.initials: M
authors.lastname: Benkißer-Petersen
authors.affiliation: 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;
authors.forename: Isabel
authors.initials: I
authors.lastname: Wilhelm
authors.affiliation: Centre for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany; Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany;
authors.forename: Sarah
authors.initials: S
authors.lastname: Villringer
authors.affiliation: Molecular Immunology Group, Cancer Sciences Unit, Cancer Research UK Centre, University of Southampton Faculty of Medicine, Southampton, United Kingdom; and.
authors.forename: Sergey
authors.initials: S
authors.lastname: Krysov
authors.affiliation: Molecular Immunology Group, Cancer Sciences Unit, Cancer Research UK Centre, University of Southampton Faculty of Medicine, Southampton, United Kingdom; and.
authors.forename: Graham
authors.initials: G
authors.lastname: Packham
authors.affiliation: Department of Hematology/Oncology, University Medical Center Freiburg, Freiburg, Germany;
authors.forename: Katja
authors.initials: K
authors.lastname: Zirlik
authors.affiliation: 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;
authors.forename: Winfried
authors.initials: W
authors.lastname: Römer
authors.affiliation: Institute for Experimental Cancer Research, Comprehensive Cancer Center Ulm, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
authors.affiliation: Molecular Immunology Group, Cancer Sciences Unit, Cancer Research UK Centre, University of Southampton Faculty of Medicine, Southampton, United Kingdom; and.
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.affiliation: 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;
authors.forename: Hassan
authors.initials: H
authors.lastname: Jumaa
mesh_terms: D001424:Bacterial Infections / Q000150:complications* / Q000276:immunology; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology*; D037102:Lectins / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000150:complications / Q000276:immunology*; D009894:Opportunistic Infections / Q000150:complications / Q000276:immunology; D011134:Polysaccharides / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D007135:Immunoglobulin Variable Region; D037102:Lectins; D011134:Polysaccharides; D011947:Receptors, Antigen, B-Cell