Abstract
BackgroundFully human monoclonal antibodies directed against specific pathogens have a high therapeutic potential, but are difficult to generate.Methodology/Principal FindingsMemory B cells were immortalized by expressing an inducible active mutant of the transcription factor Signal Transducer and Activator of Transcription 5 (STAT5). Active STAT5 inhibits the differentiation of B cells while increasing their replicative life span. We obtained cloned B cell lines, which produced antibodies in the presence of interleukin 21 after turning off STAT5. We used this method to obtain monoclonal antibodies against the model antigen tetanus toxin.Conclusions/SignificanceHere we describe a novel and relatively simple method of immortalizing antigen-specific human B cells for isolation of human monoclonal antibodies. These results show that STAT5 overexpression can be employed to isolate antigen specific antibodies from human memory B cells.
Highlights
Vaccination is a safe and efficient way to protect the human body against specific pathogens
We extended these findings by showing that constitutive activation of Signal Transducer and Activator of Transcription 5 (STAT5) in B cells led to loss of antibody surface expression when cultures were maintained for more than 6 weeks in the presence of IL-2 and IL-4 [17]
We investigated whether we could exploit the immortalizing capacity of active STAT5 mutants in order to obtain human monoclonal B cell lines, which secrete antigen specific antibodies
Summary
Vaccination is a safe and efficient way to protect the human body against specific pathogens. The use of sera enriched for pathogen-specific antibodies has been suggested [1,2]. Treatment with pathogen-specific antibodies could be applied in a prophylactic as well as in a therapeutic setting. Non-human derived sera often provoke an immune response, thereby limiting the maximum number of treatments. Other possible caveats are the fact that it is difficult to obtain large amounts of sera of the same quality, and the risk of contamination with pathogens, in particular with viruses such as but not limited to Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). Human monoclonal antibodies directed against specific pathogens have a high therapeutic potential, but are difficult to generate
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