Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen

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dc.contributor.authorKlose, Diana
dc.contributor.authorSaunders, Ute
dc.contributor.authorBarth, Stefan
dc.contributor.authorFischer, Rainer
dc.contributor.authorJacobi, Annett M
dc.contributor.authorNachreiner, Thomas
dc.date.accessioned2016-06-07T07:44:29Z
dc.date.available2016-06-07T07:44:29Z
dc.date.issued2016-02-17
dc.date.updated2016-05-18T15:49:04Z
dc.description.abstractBackground: In an earlier study we developed a unique strategy allowing us to specifically eliminate antigenspecific murine B cells via their distinct B cell receptors using a new class of fusion proteins. In the present work we elaborated our idea to demonstrate the feasibility of specifically addressing and eliminating human memory B cells. Results: The present study reveals efficient adaptation of the general approach to selectively target and eradicate human memory B cells. In order to demonstrate the feasibility we engineered a fusion protein following the principle of recombinant immunotoxins by combining a model antigen (tetanus toxoid fragment C, TTC) for B cell receptor targeting and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA’) to induce apoptosis after cellular uptake. The TTC-ETA’ fusion protein not only selectively bound to a TTC-reactive murine B cell hybridoma cell line in vitro but also to freshly isolated human memory B cells from immunized donors ex vivo. Specific toxicity was confirmed on an antigen-specific population of human CD27+ memory B cells. Conclusions: This protein engineering strategy can be used as a generalized platform approach for the construction of therapeutic fusion proteins with disease-relevant antigens as B cell receptor-binding domains, offering a promising approach for the specific depletion of autoreactive B-lymphocytes in B cell-driven autoimmune diseases.en_ZA
dc.identifier.apacitationKlose, D., Saunders, U., Barth, S., Fischer, R., Jacobi, A. M., & Nachreiner, T. (2016). Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen. <i>BMC Biotechnology</i>, http://hdl.handle.net/11427/19927en_ZA
dc.identifier.chicagocitationKlose, Diana, Ute Saunders, Stefan Barth, Rainer Fischer, Annett M Jacobi, and Thomas Nachreiner "Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen." <i>BMC Biotechnology</i> (2016) http://hdl.handle.net/11427/19927en_ZA
dc.identifier.citationKlose, D., Saunders, U., Barth, S., Fischer, R., Jacobi, A. M., & Nachreiner, T. (2016). Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen. BMC biotechnology, 16(1), 18.en_ZA
dc.identifier.issn1472-6750en_ZA
dc.identifier.ris TY - Journal Article AU - Klose, Diana AU - Saunders, Ute AU - Barth, Stefan AU - Fischer, Rainer AU - Jacobi, Annett M AU - Nachreiner, Thomas AB - Background: In an earlier study we developed a unique strategy allowing us to specifically eliminate antigenspecific murine B cells via their distinct B cell receptors using a new class of fusion proteins. In the present work we elaborated our idea to demonstrate the feasibility of specifically addressing and eliminating human memory B cells. Results: The present study reveals efficient adaptation of the general approach to selectively target and eradicate human memory B cells. In order to demonstrate the feasibility we engineered a fusion protein following the principle of recombinant immunotoxins by combining a model antigen (tetanus toxoid fragment C, TTC) for B cell receptor targeting and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA’) to induce apoptosis after cellular uptake. The TTC-ETA’ fusion protein not only selectively bound to a TTC-reactive murine B cell hybridoma cell line in vitro but also to freshly isolated human memory B cells from immunized donors ex vivo. Specific toxicity was confirmed on an antigen-specific population of human CD27+ memory B cells. Conclusions: This protein engineering strategy can be used as a generalized platform approach for the construction of therapeutic fusion proteins with disease-relevant antigens as B cell receptor-binding domains, offering a promising approach for the specific depletion of autoreactive B-lymphocytes in B cell-driven autoimmune diseases. DA - 2016-02-17 DB - OpenUCT DO - 10.1186/s12896-016-0249-x DP - University of Cape Town J1 - BMC Biotechnology KW - B cell receptor KW - Targeted therapy KW - Recombinant fusion protein KW - Periplasmic protein expression KW - Tetanus toxoid fragment C KW - Memory B cells LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 SM - 1472-6750 T1 - Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen TI - Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen UR - http://hdl.handle.net/11427/19927 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1186/s12896-016-0249-x
dc.identifier.urihttp://hdl.handle.net/11427/19927
dc.identifier.vancouvercitationKlose D, Saunders U, Barth S, Fischer R, Jacobi AM, Nachreiner T. Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen. BMC Biotechnology. 2016; http://hdl.handle.net/11427/19927.en_ZA
dc.languageengen_ZA
dc.language.rfc3066en
dc.publisherBioMed Centralen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)*
dc.rights.holderKlose et al.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_ZA
dc.sourceBMC Biotechnologyen_ZA
dc.source.urihttp://bmcbiotechnol.biomedcentral.com/
dc.subjectB cell receptor
dc.subjectTargeted therapy
dc.subjectRecombinant fusion protein
dc.subjectPeriplasmic protein expression
dc.subjectTetanus toxoid fragment C
dc.subjectMemory B cells
dc.titleNovel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigenen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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