Title |
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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Published in |
BMC Biotechnology, February 2016
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DOI | 10.1186/s12896-016-0249-x |
Pubmed ID | |
Authors |
Diana Klose, Ute Saunders, Stefan Barth, Rainer Fischer, Annett Marita Jacobi, Thomas Nachreiner |
Abstract |
In an earlier study we developed a unique strategy allowing us to specifically eliminate antigen-specific 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Science communicators (journalists, bloggers, editors) | 1 | 50% |
Members of the public | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 29 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 6 | 21% |
Researcher | 5 | 17% |
Student > Master | 4 | 14% |
Other | 3 | 10% |
Student > Ph. D. Student | 3 | 10% |
Other | 4 | 14% |
Unknown | 4 | 14% |
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Biochemistry, Genetics and Molecular Biology | 5 | 17% |
Immunology and Microbiology | 4 | 14% |
Medicine and Dentistry | 3 | 10% |
Agricultural and Biological Sciences | 2 | 7% |
Computer Science | 1 | 3% |
Other | 6 | 21% |
Unknown | 8 | 28% |