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

Blood 2015 May 17;125(21):3287-96. Epub 2015 Mar 17.

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;

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.

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2014-11-609404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482265PMC
May 2015

Publication Analysis

Top Keywords

cognate antigen
8
bcr expression
8
follicular lymphoma
8
lectins
5
bcr
5
disrupting heavy-chain
4
n-linked variable-region
4
investigated n-linked
4
lectins investigated
4
mannose-specific lectins
4
binding sites
4
sites mannose-specific
4
variable-region glycosylation
4
lectins origins
4
origins n-glycans
4
n-glycans severely
4
antigen lectins
4
genes disrupting
4
glycosylation bcr
4
bcr interaction
4

Similar Publications

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

Proc Natl Acad Sci U S A 2010 Oct 11;107(43):18587-92. Epub 2010 Oct 11.

Molecular Immunology Group, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton SO16 6YD, United Kingdom.

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. Read More

View Article and Full-Text PDF
October 2010

A spoonful of sugar helps lymphoma cells go up.

Blood 2015 May;125(21):3215-6

THE FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH.

View Article and Full-Text PDF
May 2015

Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor.

J Biol Chem 2007 Mar 29;282(10):7405-15. Epub 2006 Dec 29.

Glycobiology Institute, Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.

Expression of surface immunoglobulin appears critical for the growth and survival of B-cell lymphomas. In follicular lymphoma, we found previously that the Ig variable (V) regions in the B-cell receptor express a strikingly high incidence of N-glycosylation sequons, NX(S/T). These potential glycosylation sites are introduced by somatic mutation and are lymphoma-specific, pointing to their involvement in tumor pathogenesis. Read More

View Article and Full-Text PDF
March 2007

DC-SIGN-expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma.

Blood 2015 Oct 13;126(16):1911-20. Epub 2015 Aug 13.

Equipe Labellisée Ligue Contre le Cancer, Unité Mixte de Recherche U917, INSERM, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France; Pôle Biologie, Centre Hospitalier Universitaire de Rennes, Rennes, France;

Follicular lymphoma (FL) results from the accumulation of malignant germinal center (GC) B cells leading to the development of an indolent and largely incurable disease. FL cells remain highly dependent on B-cell receptor (BCR) signaling and on a specific cell microenvironment, including T cells, macrophages, and stromal cells. Importantly, FL BCR is characterized by a selective pressure to retain surface immunoglobulin M (IgM) BCR despite an active class-switch recombination process, and by the introduction, in BCR variable regions, of N-glycosylation acceptor sites harboring unusual high-mannose oligosaccharides. Read More

View Article and Full-Text PDF
October 2015