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July 17th, 2025
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University of Southampton
cancer biology
biorxiv

DC-SIGN Binding to the Surface Ig Oligomannose-type Glycans Promotes Follicular Lymphoma Cell Adhesion and Survival

Chiodin, G.Open in Google Scholar•Tatterton, D. J.Open in Google Scholar•Rock, P. J.Open in Google Scholar•del Rio, L.Open in Google Scholar•Snook, E. L.Open in Google Scholar•James, S.Open in Google Scholar•Duriez, P. J.Open in Google Scholar•Di Re, M.Open in Google Scholar•Verdoes, M.Open in Google Scholar•Lanham, S.Open in Google Scholaret al.

The occupation of the surface immunoglobulin antigen-binding site by oligomannose-type glycans (sIg-Mann) is a tumor-specific post-translational modification of classic follicular lymphoma (FL). SIg-Mann switches binding from antigen to dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN), known to be expressed on interfollicular macrophages and FL-associated follicular dendritic cells (FDCs). The interaction with DC-SIGN induces reorganization of sIg-Mann in wider and less dense clusters than anti-Ig, consistent with inefficient DC-SIGN-induced endocytosis and a low-level intracellular signaling. However, ligand-specific cell clusters form between sIg-Mann-expressing lymphoma and DC-SIGN-expressing cells, raising a need to understand the functional consequences of the interaction of DC-SIGN with sIg-Mann on primary FL cells. This engagement induces adhesion of FL cells to VCAM-1 via B-cell receptor proximal kinases and actin regulators in a fashion similar to anti-Ig, but without initiating apoptosis in vitro. Instead, antibody blockade of sIg-Mann contact with DC-SIGN expressed on FDC-derived YK6/SIGN cells inhibits adhesion and survival of primary FL cells in vitro. These data highlight that the specific interaction with DC-SIGN induces FL cell adhesion to VCAM-1, likely allowing FL cell retention in the lymph node, and survival of the FL cells. Adhesion and survival are inhibited by an anti-DC-SIGN blocking antibody, indicating a new early therapeutic approach against FL retention and survival in adaptive tumor tissue niches.

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