Natural antibody recognition, signaling and surveillance in v-Ha-ras- and PKC-B1-overexpressing 10T1/2 fibroblasts
| dc.contributor.author | Wang, Hongsheng | en_US |
| dc.date.accessioned | 2007-05-18T12:12:47Z | |
| dc.date.available | 2007-05-18T12:12:47Z | |
| dc.date.issued | 1998-05-01T00:00:00Z | en_US |
| dc.degree.discipline | Immunology | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Extensive evidence supports a role for polyclonal serum natural antibody (NAb) acting as a mediator of natural resistance against tumors in mice. However, little is known about its mechanisms of action or about the phenotype of susceptible cells. C3H 10T${1\over 2}$ fibroblasts overexpressing an activated ras oncogene or a PKC-$\beta$1 gene increased their NAb binding capacities, identifying PKC, an integral signaling molecule of normal cellular activation, as a key regulator of NAb binding structures. This, coupled with corresponding decreases in expression of membrane PKC-$\alpha$ and NAb binding in resting confluent 10T${1\over 2}$ cells raised the possibility that, in general, cells activated through PKC are NAb sensitive. In addition, NAb interaction with 10T${1\over 2}$ variants initiated a signal transduction mechanism including activation of PKC, shedding of cell surface molecules and bound NAb, a reduction in phosphotyrosine levels of a membrane-associated 60 KDa molecule, and, over time, the inhibition of DNA synthesis. Together with the increased in vivo elimination of the high NAb binding PKC-$\beta$1-overexpressing cells and the beneficial effect of passive syngeneic NAb in the rejection of syngeneic tumors injected s.c. and i.v. in both xid-bearing B cell deficient and B cell normal mouse models, the data argued that NAb not only participates in tumor surveillance of preneoplasia and neoplasia but contributes to homeostasis of the organism. | en_US |
| dc.format.extent | 13892530 bytes | |
| dc.format.extent | 184 bytes | |
| dc.format.mimetype | application/pdf | |
| dc.format.mimetype | text/plain | |
| dc.identifier.uri | http://hdl.handle.net/1993/1574 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.title | Natural antibody recognition, signaling and surveillance in v-Ha-ras- and PKC-B1-overexpressing 10T1/2 fibroblasts | en_US |
| dc.type | doctoral thesis | en_US |