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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 i...

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Autores principales: Frensch, Marco, Jäger, Christina, Müller, Peter F., Tadić, Annamaria, Wilhelm, Isabel, Wehrum, Sarah, Diedrich, Britta, Fischer, Beate, Meléndez, Ana Valeria, Dengjel, Joern, Eibel, Hermann, Römer, Winfried
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629787/
https://www.ncbi.nlm.nih.gov/pubmed/34731252
http://dx.doi.org/10.1007/s00018-021-04009-z
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author Frensch, Marco
Jäger, Christina
Müller, Peter F.
Tadić, Annamaria
Wilhelm, Isabel
Wehrum, Sarah
Diedrich, Britta
Fischer, Beate
Meléndez, Ana Valeria
Dengjel, Joern
Eibel, Hermann
Römer, Winfried
author_facet Frensch, Marco
Jäger, Christina
Müller, Peter F.
Tadić, Annamaria
Wilhelm, Isabel
Wehrum, Sarah
Diedrich, Britta
Fischer, Beate
Meléndez, Ana Valeria
Dengjel, Joern
Eibel, Hermann
Römer, Winfried
author_sort Frensch, Marco
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-04009-z.
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spelling pubmed-86297872021-12-15 Bacterial lectin BambL acts as a B cell superantigen Frensch, Marco Jäger, Christina Müller, Peter F. Tadić, Annamaria Wilhelm, Isabel Wehrum, Sarah Diedrich, Britta Fischer, Beate Meléndez, Ana Valeria Dengjel, Joern Eibel, Hermann Römer, Winfried Cell Mol Life Sci Original Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-04009-z. Springer International Publishing 2021-11-03 2021 /pmc/articles/PMC8629787/ /pubmed/34731252 http://dx.doi.org/10.1007/s00018-021-04009-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Frensch, Marco
Jäger, Christina
Müller, Peter F.
Tadić, Annamaria
Wilhelm, Isabel
Wehrum, Sarah
Diedrich, Britta
Fischer, Beate
Meléndez, Ana Valeria
Dengjel, Joern
Eibel, Hermann
Römer, Winfried
Bacterial lectin BambL acts as a B cell superantigen
title Bacterial lectin BambL acts as a B cell superantigen
title_full Bacterial lectin BambL acts as a B cell superantigen
title_fullStr Bacterial lectin BambL acts as a B cell superantigen
title_full_unstemmed Bacterial lectin BambL acts as a B cell superantigen
title_short Bacterial lectin BambL acts as a B cell superantigen
title_sort bacterial lectin bambl acts as a b cell superantigen
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629787/
https://www.ncbi.nlm.nih.gov/pubmed/34731252
http://dx.doi.org/10.1007/s00018-021-04009-z
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