The α2,3 sialyltransferase ST3Gal1 regulates galectin-3 binding to human B cells

Activated leukocytes commonly remodel cell surface carbohydrates (glycans) in order to modulate lectin-glycoprotein interactions involved in trafficking, adhesion, antigen receptor signaling, and cell fate. Because germinal center (GC) B cells upregulate glycan ligands for peanut lectin (PNA), we hypothesized that B cells remodel cell surface glycans upon GC differentiation in order to alter interactions with endogenous lectins. To test this, we studied cell surface glycosylation of ex vivo tonsillar naive, GC, memory, and plasmablast (PB) B cells using a panel of lectin probes. We found that in addition to PNA ligands, polylactosamine chains (polyLNs) are u003e4-fold enriched on GC B cells compared to naive, memory, and PB subsets, and that polyLNs are predominantly present as O-glycans on CD45. Moreover, qRT-PCR analysis and overexpression studies in tonsil and Ramos B cells, respectively, revealed polyLNs are inversely correlated with expression of ST3Gal1, an α2,3 sialyltransferase that competes for polyLN precursors. Given that polyLNs are preferred ligands of galectin-3 (Gal-3), a known regulator of apoptosis enriched in GCs, we assessed whether ST3Gal1 regulates Gal-3 binding to B cells. Unexpectedly, B cells with the lowest ST3Gal1 expression and most polyLNs (GC, ST3Gal1 lo Ramos B cells) showed poor Gal3 binding, whereas B cells with natively high or enforced ST3Gal1 expression (Naive, Memory, ST3Gal1 hi Ramos B cells) exhibited robust Gal-3 binding. Thus, our data implicate ST3Gal1 as a novel regulator of Gal-3 binding in B cells by a non-canonical mechanism. We propose GC B cells reduce Gal-3 ligand expression by repressing ST3Gal1 transcription, and as a result tune CD45-related signaling and susceptibility to apoptosis.