Lectins from Opportunistic Bacteria Interact with Acquired Variable-region Glycans of Surface Immunoglobulin in Follicular Lymphoma

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2015 Mar 19

PMID 25784678

Citations 33

Authors

Dunja Schneider

Marcus Duhren-von Minden

Alabbas Alkhatib

Corinna Setz

Cornelis A M van Bergen

Marco Benkisser-Petersen

Isabel Wilhelm

Sarah Villringer

Sergey Krysov

Graham Packham

Katja Zirlik

Winfried Romer

Christian Buske

Freda K Stevenson

Hendrik Veelken

Hassan Jumaa

Affiliations

Soon will be listed here.

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.

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