Interactions of antibodies and their derivatives with leukaemia cell surfaces
Interactions of antibodies and their derivatives with leukaemia cell surfaces
Studies have been made of the effects of the interaction of antibodies with the surface immunoglobulin of guinea pig L2C B-lymphoblastic leukaemia cells. Firstly, investigations were made into the behaviour of the surface immunoglobulin both in the absence and presence of such antibodies, and secondly extensive studies were undertaken into the effects of accessory cells upon the ability of such antibodies to induce modulation (the redistribution and internalization) of the surface immunoglobulin. In the first section use was made of a system in which the fate of the surface immunoglobulin could be traced without its ligation in situ with antibodies. These studies showed that the surface immunoglobulin was being continuously internalized by the L2C cells, and suggested that some recycling of the surface immunoglobulin may occur. The effects of univalent and bivalent fragments of anti-immunoglobulin antibodies were then studied. Univalent fragments did not induce any modulation of the surface immunoglobulin, but were continuously internalized at a slow rate. They were not degraded within the cell to any detectable extent. In contrast, bivalent fragments induced rapid modulation of the surface immunoglobulin and were extensively degraded within the cell. In the second section it was demonstrated that the in vitro modulation of L2C cell surface immunoglobulin induced by anti-immunoglobulin antibodies was enhanced in the presence of isolated guinea pig Kupffer cells. It was also shown that univalent antibody derivatives containing Fc regions were able to induce modulation in vitro only in the presence of Kupffer cells. Further studies showed that this was due to the physical interaction of the Kupffer cells with the antibody-coated cells, via the Fc portion of the antibody and the Fc receptors on the Kupffer cell surface. Modulation enhancement was mediated by all of the Fcγ receptors studied on guinea pig, rat and human cells. The degree of modulation enhancement was related to the level of Fc receptors on the accessory cell surface. Functional studies indicated that modulation enhancement resulted in significant protection of the tumour cells from complement-mediated lysis. It was shown using antibodies to other cell surface antigens on human cell lines that modulation enhancement occurred with all three antigens studied. In vivo studies into the effects of anti-immunoglobulin treatment of leukaemic guinea pigs demonstrated that tumour cells were rapidly cleared from the circulation by bivalent reagents and also by an Fc containing univalent derivative. However only reagents containing Fc regions induced surface immunoglobulin modulation in vivo to any greater extent than in vitro, demonstrating the importance of in vivo modulation enhancement by Fc receptor bearing cells.
University of Southampton
1989
Lane, Andrew Charles
(1989)
Interactions of antibodies and their derivatives with leukaemia cell surfaces.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Studies have been made of the effects of the interaction of antibodies with the surface immunoglobulin of guinea pig L2C B-lymphoblastic leukaemia cells. Firstly, investigations were made into the behaviour of the surface immunoglobulin both in the absence and presence of such antibodies, and secondly extensive studies were undertaken into the effects of accessory cells upon the ability of such antibodies to induce modulation (the redistribution and internalization) of the surface immunoglobulin. In the first section use was made of a system in which the fate of the surface immunoglobulin could be traced without its ligation in situ with antibodies. These studies showed that the surface immunoglobulin was being continuously internalized by the L2C cells, and suggested that some recycling of the surface immunoglobulin may occur. The effects of univalent and bivalent fragments of anti-immunoglobulin antibodies were then studied. Univalent fragments did not induce any modulation of the surface immunoglobulin, but were continuously internalized at a slow rate. They were not degraded within the cell to any detectable extent. In contrast, bivalent fragments induced rapid modulation of the surface immunoglobulin and were extensively degraded within the cell. In the second section it was demonstrated that the in vitro modulation of L2C cell surface immunoglobulin induced by anti-immunoglobulin antibodies was enhanced in the presence of isolated guinea pig Kupffer cells. It was also shown that univalent antibody derivatives containing Fc regions were able to induce modulation in vitro only in the presence of Kupffer cells. Further studies showed that this was due to the physical interaction of the Kupffer cells with the antibody-coated cells, via the Fc portion of the antibody and the Fc receptors on the Kupffer cell surface. Modulation enhancement was mediated by all of the Fcγ receptors studied on guinea pig, rat and human cells. The degree of modulation enhancement was related to the level of Fc receptors on the accessory cell surface. Functional studies indicated that modulation enhancement resulted in significant protection of the tumour cells from complement-mediated lysis. It was shown using antibodies to other cell surface antigens on human cell lines that modulation enhancement occurred with all three antigens studied. In vivo studies into the effects of anti-immunoglobulin treatment of leukaemic guinea pigs demonstrated that tumour cells were rapidly cleared from the circulation by bivalent reagents and also by an Fc containing univalent derivative. However only reagents containing Fc regions induced surface immunoglobulin modulation in vivo to any greater extent than in vitro, demonstrating the importance of in vivo modulation enhancement by Fc receptor bearing cells.
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Published date: 1989
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Local EPrints ID: 460533
URI: http://eprints.soton.ac.uk/id/eprint/460533
PURE UUID: 9afe1c28-cce1-4107-8ac2-c48954d248a8
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Date deposited: 04 Jul 2022 18:24
Last modified: 04 Jul 2022 18:24
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Author:
Andrew Charles Lane
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