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

Area of Science:

• Immunology
• Glycobiology
• Cell Biology

Background:

• Galectins are proteins that bind carbohydrates (glycans) on cell surfaces, influencing immunity, cell migration, and signaling.
• Galectins also bind non-glycosylated proteins, such as the pre-B cell receptor (pre-BCR) during B cell development, but how this affects their glycan-binding function is unclear.

Purpose of the Study:

• To investigate how interactions with non-glycosylated partners, specifically the pre-B cell receptor (pre-BCR), modulate the glycan-binding activity of galectin-1 (Gal-1).
• To identify the molecular mechanisms and specific glycan structures involved in this modulation and its impact on B cell development.

Main Methods:

• Nuclear Magnetic Resonance (NMR) experiments were conducted on native cell membranes to observe Gal-1 binding to cell surface ligands.
• Molecular and cellular assays were used to identify specific glycan targets and assess the functional consequences of Gal-1-pre-BCR interactions.

Main Results:

• Pre-BCR interaction was shown to alter Gal-1 binding to glycosylated receptors on pre-B cells.
• A selectivity switch was identified, increasing Gal-1's affinity for α2,3-sialylated poly-N-acetyllactosamine motifs upon pre-BCR engagement.
• This switch was found to be critical for regulating pre-BCR activation during B cell development.

Conclusions:

• Interactions with non-glycosylated proteins, exemplified by the pre-BCR, dynamically regulate the glycan-decoding capabilities of galectins at the cell surface.
• This provides a novel mechanism by which protein-protein interactions can fine-tune galectin function in physiological processes like immune cell development.