Bacterial lectin BambL acts as a B cell superantigen.

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.

Mitotic activity, modulation of DNA processing, and purinergic signalling in the adult rat auditory brainstem following sensory deafferentation.

A complex scenario of cellular network reorganization is caused by unilateral sensory deafferentation (USD) in the adult rat central auditory system. We asked whether this plasticity response involves mitosis. Immunohistochemistry was applied to brainstem sections for the detection and localization of mitotic markers Ki67 and PCNA, the growth-associated protein Gap43 and purine receptor P2X4. Fluorescent double staining was done for Ki67:PCNA and for both of them with HuC/HuD (neurons), S100 (astrocytes), Iba1 (microglia) and P2X4. Inquiring 1-7 days after USD, we found Ki67 expression to be changed in cellular profiles of cochlear nucleus (CN) with a significant increase in number by 1-3 days, followed by reset to control level within 1 week. USD-induced mitosis exclusively occurred in microglia and was absent elsewhere in the auditory brainstem. PCNA staining of small cellular profiles increased similarly but remained elevated. PCNA staining intensity also changed in CN, superior olive and inferior colliculus in neuronal nuclei, suggesting shifts in DNA processing. No apoptotic cell death was detected in any region of the adult auditory brainstem after USD. A comparison of anterograde and retrograde effects of nerve damage revealed proliferating microglia expressing P2X4 receptors in CN upon USD, but not in the facial nucleus after facial nerve transection. In conclusion, the deafferentation model studied here permits insight into the capacity of the adult mammalian brain to invoke mitosis among glia cells, adjustment of gene processing in neurons and purinergic signalling between them, jointly accounting for a multilayered neuro- and glioplastic response.