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Molecular characterization of patient-derived Follicular Lymphoma and Chronic Lymphocytic Leukemia B cell receptor variable domain glycans

ABSTRACT: Follicular lymphoma (FL) is a systemic, lymphoid tissue-derived neoplasm of germinal center phenotype B cells that have undergone a t(14;18) chromosomal translocation. A remarkable feature of B cell receptors (BCRs) expressed by FL B cells is the presence of variable domain N-linked glycosylation sites, which are introduced during a process called somatic hypermutation. These novel glycosylation sites are preferentially located in specific ‘hotspot’ sites and are suggested to play a role in the survival of FL B cells, feasibly via the interactions between the N-glycans that occupy these sites and environmental lectins. Thus far, in-depth, molecular characterization of patient-derived, primary FL BCR variable domain glycans (VDGs) has not been performed. In this report, using liquid chromatography-mass spectrometry, we assess the glycosylation profiles of 14 VDG sites from 9 unique patient-derived tumors, and as a comparator, include 3 patient-derived chronic lymphocytic leukemia B cell clones, each harboring a VDG site. We show that FL BCR heavy chain VDG are enriched in oligomannose-type glycans and show using molecular dynamics simulations, that the level of glycan processing correlates with the accessibility of glycosidase ERManI to the glycosylation site and is additionally affected by steric hindrance from neighboring glycans.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell

DISEASE(S): Lymphoma

SUBMITTER: Rayman Tjokrodirijo

LAB HEAD: Peter A. van Veelen

PROVIDER: PXD073349 | Pride | 2026-01-23

REPOSITORIES: Pride

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	E20232001248a.raw	Raw
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