PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / The purpose of this research project was to examine the capacity of anti-idiotypic antibodies and anti-idiotypic-like antibodies to regulate normal and malignant B-cell populations. Out of this project stemmed two new findings. The first was a technique for the rapid comparison of the primary amino acid sequences of antibody molecules. This method was applied to studying a panel of antibodies derived from an immune response characterized by a dominant idiotype where it was able to quickly distinguish between idiotype positive antibodies that differed by only a few amino acids. The technique was also applied to the analysis of monoclonal antibodies derived from fusions between human B-cell tumor containing tissue and mouse myeloma cells in order to identify which hybridomas were derived from the malignant B-cell population. The second finding involved techniques for growing non-murine antibody secreting hybridomas in immunosuppressed mice. Human x mouse and rat x mouse heterohybridomas grew readily in mice treated with cortisone and radiation but completely xenogeneic (rat x rat) hybrids did not. This was overcome by developing a ouabain resistant variant of the SP-2 mouse myeloma cell line and fusing it to the (rat x rat) hybridomas forming a "second generation" hybridoma cell lines that grew readilly in immunosuppressed mice. As an outgrowth of the human anti-idiotype project came an idiotype-like regulation model system. The idiotype-like regulation project was an attempt to extend the idiotype specific regulation effects of anti-idiotypic antibodies to the entire antigen binding antibody response. An antibody construct was made by covalently coupling antibodies specific for photoligand moiety to a peptide consisting of a photoligand attached to a hapten. The resulting complex had a single hapten specifically bound to each antigen binding region of the monoclonal antibody and was expected to influence antigen binding B-cells in much the same way as an anti-idiotypic antibody. However, when these complexes were injected into mice it was found that they did not modulate the subsequent antibody response. This lack of effect was due to a greatly decreased circulation time of the antibody-photoligand-hapten complex.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/45248 |
| Date | January 1987 |
| Creators | Weissman, Drew |
| Publisher | Boston University |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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