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

作者：Schneider Dunja; Duehren von Minden Marcus; Alkhatib Alabbas; Setz Corinna; van Bergen Cornelis A M; Benkisser Petersen Marco; Wilhelm Isabel; Villringer Sarah; Krysov Sergey; Packham Graham; Zirlik Katja; Roemer Winfried; Buske Christian; Stevenson Freda K; Veelken Hendrik; Jumaa Hassan^*

来源：Blood, 2015, 125(21): 3287-3296.

DOI：10.1182/blood-2014-11-609404

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 bindingsites formannose-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.

• 出版日期2015-5-21