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

Abstract

Galectins are glycan binding proteins translating the sugar-encoded information of cellular glycoconjugates into many physiological activities including immunity, cell migration, and signaling. During early B lymphocytes (BL) development at the pre-B cell stage, BL express the pre-B cell receptor (pre-BCR) and are supported by mesenchymal stromal cells secreting Galectin-1 (Gal-1). Gal-1 interacts with glycosylated receptors from stromal and pre-B cell surfaces but also with the pre-BCR through a direct carbohydrate-independent contact. How this interaction might interplay with the glycan-decoding function of Gal-1 is unknown. Here, we investigated Gal-1 binding to cell surface ligands using NMR spectroscopy on native membranes. We showed that pre-BCR regulates Gal-1 binding to specifically target α2,3-sialylated receptors on pre-B cells. Upon pre-BCR interaction, dynamic changes resulted in additional contacts with α2,3-sialylated glycans converting Gal-1 from an exo- to an endo-type lectin. Remarkably, this selectivity switch is able to promote pre-B cell survival. Altogether, we shed light on a new mechanism allowing fine-tuning of Galectin specificity at the cell surfaces.

The role of N-glycosylation in B-cell biology and IgG activity. The aspects of autoimmunity and anti-inflammatory therapy

“…Galectin (gal), a galactose-binding protein, also plays an important role in B-cell development (39). At an early stage of maturation, pre-B cells localise in niches with mesenchymal stromal cells secreting gal-1.…”

“…In addition, the interaction of gal-1 with SA a2,3-bound glycans resulted in the dynamic conversion of galectin from an exogenous to an endogenous type lectin. Importantly, this selectivity switch can keep pre-B cells alive (39). A recent study focused on analyzing the N-glycan pool of human naive tonsil, germinal center (GC) and memory B cells using mass spectrometry and flow cytometry, based on labeling the cells with lectins that recognize specific sugar residues.…”