Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma
17.03.2015
Schneider D, Dühren-von Minden M, Alkhatib A, Setz C, van Bergen CA, Benkisser-Petersen M, Wilhelm I, Villringer S, Krysov S, Packham G, Zirlik K, Römer W, Buske C, Stevenson FK, Veelken H, Jumaa H.
Blood. 2015;125(21):3287-96
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 auto-antigen recognition remain unclear. In follicular lymphoma (FL) B cells BCR expression is retained despite a chromosomal translocation that links the anti-apoptotic gene BCL2 to the regulatory elements of immunoglobulin genes thereby disrupting one 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.
