Carbohydrate-dependent B cell activation by fucose-binding bacterial lectins

Abstract

Bacterial lectins are typically multivalent and bind noncovalently to specific carbohydrates on host tissues to facilitate bacterial adhesion. Here, we analyzed the effects of two fucose-binding lectins, BambL from Burkholderia ambifaria and LecB from Pseudomonas aeruginosa, on specific signaling pathways in B cells. We found that these bacterial lectins induced B cell activation, which, in vitro, was dependent on the cell surface expression of the B cell antigen receptor (BCR) and its co-receptor CD19, as well as on spleen tyrosine kinase (Syk) activity. The resulting release of intracellular Ca 2+ was followed by an increase in the cell surface abundance of the activation marker CD86, augmented cytokine secretion, and subsequent cell death, replicating all of the events that are observed in vitro upon canonical and antigen-mediated B cell activation. Moreover, injection of BambL in mice resulted in a substantial, BCR-independent loss of B cells in the bone marrow with simultaneous, transient enlargement of the spleen (splenomegaly), as well as an increase in the numbers of splenic B cells and myeloid cells. Together, these data suggest that bacterial lectins can initiate polyclonal activation of B cells through their sole capacity to bind to fucose.

Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation

“…Although in that study we did not measure DSA, it is interesting to speculate that Pseudomonas aeruginosa‐ mediated neutrophil B7 upregulation could bolster CD28‐mediated CD4 + T cell help to B cells to promote DSA generation in a similar manner. Ultimately, the inflammatory environment induced by Pseudomonas aeruginosa may promote the clonal expansion of alloreactive T cells and the polyclonal activation of B cells, and upregulation of HLA molecules on airway epithelial cells to amplify the humoral alloimmune response. Pseudomonas aeruginosa is also capable of facilitating affinity maturation and promoting isotype switching and somatic mutations in alloreactive B cells, especially if these antigens are already exposed on the allograft .…”

Anti-biofilm Agents against Pseudomonas aeruginosa: A Structure–Activity Relationship Study of C-Glycosidic LecB Inhibitors

“…Besides its role in biofilm formation and bacterial adhesion, LecB was also shown to carbohydrate-dependently block human ciliary beating, 25 interfere with tissue repair processes 26 and, recently, activate B-cells. 27 Furthermore, a direct involvement of LecA and LecB in infection and host colonization by P. aeruginosa using a murine infection model revealed the suitability of both lectins as therapeutic targets. 28,29 Inhalation of an aerosol of fucose and galactose, the ligands of LecB and LecA, resulted in a reduction of bacterial load in human infected airways 30,31 and in mice.…”

Directing Drugs to Bugs: Antibiotic-Carbohydrate Conjugates Targeting Biofilm-Associated Lectins of Pseudomonas aeruginosa

“… 19 Further, both lectins also play roles in the direct infection process: LecB conveys virulence through carbohydrate-dependent inhibition of human ciliary beating, 20 interference with repair of wounded tissues, 21 , 22 and activation of B-cells. 23 Next to its biofilm-related roles, it was shown that the d -galactose-binding LecA triggers host cell signaling pathways 24 and mediates membrane invaginations after binding to its cellular receptor, the glycosphingolipid Gb3. 25 In vivo , both proteins are involved in the P. aeruginosa infection process and host colonization in a murine infection model.…”