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Further processing of the glycan is blocked by complementarity-determining region\u2013specific steric hindrance, leading to exposure of mannosylated immunoglobulin (Ig) to the microenvironment. This allows for interaction with the local lectin, dendritic cell\u2013specific ICAM-3\u2013grabbing nonintegrin (DC-SIGN), expressed by tissue macrophages and follicular dendritic cells. The major function of DC-SIGN is to engage pathogens, but this is subverted by FL cells. DC-SIGN induces tumor-specific low-level BCR signaling in FL cells and promotes membrane changes with increased adhesion to VCAM-1 via proximal kinases and actin regulators but, in contrast to engagement by anti-Ig, avoids endocytosis and apoptosis. These interactions appear mandatory for the early development of FL, before the acquisition of other accelerating mutations. BCR-associated mannosylation can be found in a subset of germinal center B-cell\u2013like diffuse large B-cell lymphoma with t(14;18), tracking these cases back to FL. This category was associated with more aggressive behavior: both FL and transformed cases and, potentially, a significant number of cases of Burkitt lymphoma, which also has sites for N-glycan addition, could benefit from antibody-mediated blockade of the interaction with DC-SIGN.<\/jats:p><\/jats:sec>","DOI":"10.1182\/blood.2023022703","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T19:31:34Z","timestamp":1700681494000},"page":"1091-1100","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":19,"title":["The essential microenvironmental role of oligomannoses specifically inserted into the antigen-binding sites of lymphoma cells"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0933-5021","authenticated-orcid":false,"given":"Freda K.","family":"Stevenson","sequence":"first","affiliation":[{"name":"School of Cancer Sciences, Faculty of Medicine, University 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