Bacterial lectin BambL acts as a B cell superantigen

Abstract

B cell superantigens crosslink conserved domains of B cell receptors (BCRs) and cause dysregulated, polyclonal B cell activation irrespective of normal BCR-antigen complementarity. The cells typically succumb to activation-induced cell death, which can impede the adaptive immune response and favor infection. In the present study, we demonstrate that the fucose-binding lectin of Burkholderia ambifaria, BambL, bears functional resemblance to B cell superantigens. By engaging surface glycans, the bacterial lectin activated human peripheral blood B cells, which manifested in the surface expression of CD69, CD54 and CD86 but became increasingly cytotoxic at higher concentrations. The effects were sensitive to BCR pathway inhibitors and excess fucose, which corroborates a glycan-driven mode of action. Interactome analyses in a model cell line suggest BambL binds directly to glycans of the BCR and regulatory coreceptors. In vitro, BambL triggered BCR signaling and induced CD19 internalization and degradation. Owing to the lectin’s six binding sites, we propose a BCR activation model in which BambL functions as a clustering hub for receptor glycans, modulates normal BCR regulation, and induces cell death through exhaustive activation.

Lectins and polysaccharide EPS I have flow-responsive roles in the attachment and biofilm mechanics of plant pathogenicRalstonia

“…In silico mutagenesis revealed that residues Arg17, Glu28, Trp76, Trp81 in intramonomeric binding sites are crucial for LecF interactions with Me-α-L-fucoside [61]. In the opportunistic human pathogen B. ambifaria , BambL functions as a B cell superantigen binding fucose on blood B cell receptors, possibly triggering activation- induced cell death and disrupting the adaptive immune response [62,63]. Lectin interactions with surface glycans on eukaryotic hosts are evidently important for pathogenesis.…”

Pseudomonas aeruginosaLecB suppresses immune responses by inhibiting transendothelial migration

“…LecB and BambL, a L‐fucose‐binding lectin from Burkholderia ambifaria , induce B cell activation and subsequent cell death in vitro . Injection of BambL into mice leads to polyclonal activation of B cells (Wilhelm et al , 2019 ; Frensch et al , 2021 ), which could thwart an efficient humoral immune response. However, on the whole, the impact of microbial lectins on the immune system has remained poorly studied.…”