Pre-B cell receptor acts as a selectivity switch for galectin-1 at the pre-B cell surface

Galectins are glycan-binding proteins translating the sugar-encoded information of cellular glycoconjugates into physiological activities, including immunity, cell migration, and signaling. Galectins also interact with non-glycosylated partners in the extracellular milieu, among which the pre-B cell receptor (pre-BCR) during B cell development. How these interactions might interplay with the glycan-decoding function of galectins is unknown. Here, we perform NMR experiments on native membranes to monitor Gal-1 binding to physiological cell surface ligands. We show that pre-BCR interaction changes Gal-1 binding to glycosylated pre-B cell surface receptors. At the molecular and cellular levels, we identify α2,3-sialylated motifs as key targeted epitopes. This targeting occurs through a selectivity switch increasing Gal-1 contacts with α2,3-sialylated poly-N-acetyllactosamine upon pre-BCR interaction. Importantly, we observe that this switch is involved in the regulation of pre-BCR activation. Altogether, this study demonstrates that interactions to non-glycosylated proteins regulate the glycan-decoding functions of galectins at the cell surface. [Display omitted] •The pre-BCR (λ5-UR) modifies Gal-1 binding to cell surface glycoconjugates•Gal-1 targets cell surface α2,3-sialylated glycoconjugates upon pre-BCR binding•Gal-1 selectivity switch occurs by increased contacts with α2,3-sialylated glycans•Targeting of α2,3-sialylated glycoconjugates by Gal-1 regulates pre-BCR signaling Touarin et al. report NMR monitoring of Gal-1 binding to cell surface ligands. They find that interaction with the pre-BCR changes Gal-1 binding to specifically target α2,3-sialylated glycoconjugates at the pre-B cell surface. This targeting regulates pre-BCR signaling, a key checkpoint during B cell development.