Bacterial lectin BambL acts as a B cell superantigen.

Area of Science:

• Immunology
• Microbiology
• Glycobiology

Background:

• B cell superantigens cause polyclonal B cell activation and subsequent cell death by crosslinking B cell receptors (BCRs).
• This dysregulated activation can impair adaptive immunity and increase susceptibility to infections.

Purpose of the Study:

• To investigate the functional resemblance of Burkholderia ambifaria lectin (BambL) to B cell superantigens.
• To elucidate the mechanism by which BambL interacts with and activates B cells.

Main Methods:

• Treatment of human peripheral blood B cells with BambL.
• Analysis of cell surface marker expression (CD69, CD54, CD86) and cytotoxicity.
• Assessment of BambL's effects using B cell receptor (BCR) pathway inhibitors and excess fucose.
• Interactome analyses in a model cell line to identify BambL binding partners.
• In vitro studies on BCR signaling and CD19 dynamics.

Main Results:

• BambL activated human B cells, increasing expression of CD69, CD54, and CD86.
• Higher BambL concentrations induced cytotoxicity, suggesting a dose-dependent effect.
• The observed effects were sensitive to BCR inhibitors and fucose, indicating a glycan-mediated mechanism.
• Interactome data suggested BambL binds to BCR and coreceptor glycans, triggering BCR signaling and CD19 degradation.

Conclusions:

• BambL functions similarly to B cell superantigens by engaging surface glycans.
• BambL acts as a clustering hub for BCR glycans, leading to modulated BCR regulation and exhaustive activation.
• This mechanism results in B cell activation and, ultimately, cell death, with implications for immune response modulation.