Diss. (sammanfattning Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

Autoantibodies are antibodies made abnormally to self-antigens that are expressed on the surface, in the cytoplasm, or in the nucleus of the cell. These antibodies are produced in certain people whose immune system has failed to work properly. It is a puzzle, however, how the B cells that produce autoantibodies which target the vital intracellular autoantigens and with potential deleterious effects to the cell, are able to exist in nature and not succumb to suicide. We have found a suitable model to answer this question. This is a newly-constructed mouse hybridoma (#476), which produces an IgG1 monoclonal antibody (mAb 476) to an epitope in the catalytic subunit of telomerase (TERT). This mAb stains TERT very well in both mouse and human cells. The unusual thing about hybridoma 476 is that, although it can grow and produce the antibody normally in culture, however, it fails repeatedly to grow in the peritoneum of normal BALB/c mice primed with an adjuvant, unlike other hybridomas of similar backgrounds that we have used. Control cell lines used in the study include a hybridoma (Mab2) which makes an IgG1 antibody to phosphorylcholine, and the myeloma fusion partner (Sp2/0) used to construct hybridoma 476. / When the antibody specificity was abrogated by genetic manipulation or by natural selection, the 476 cells were able to grow and produce ascites in vivo normally. This shows that the problem was specific, due to binding of the mAb with its antigen, TERT. Telomerase is a housekeeping enzyme in cells essential for maintaining the stability of the telomere, the DNA repeats found at the ends of chromosomes, failing which the cell undergoes senescence and eventually dies. It appeared that the peritoneum, unlike the culture medium, contained factors that presumably up-regulated the antibody production in the cells, which consequently increased the complex formation between TERT and mAb 476 in these cells, and led to cell apoptosis. Indeed, examination of the culture supernatant ("soup") of the peritoneal cells harvested from the adjuvant-primed mice, revealed no cytotoxic cytokines or chemokines present, but an abundant amount of IL-6. In parental 476 cells in culture, both soup and purified recombinant IL-6 were found to up-regulate the production of the intracellular antibodies, but not the secreted antibodies. The effect of these reagents on the Mab2 cells was different; both the intracellular and secreted antibodies were increased. (Abstract shortened by UMI.) / Niu Haitao. / "April 2005." / Adviser: Pak-Leong Lim. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0169. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 199-228). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.