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dc.contributor.advisorDavid C. Parker
dc.contributor.authorBaird, Allison Michelle
dc.date2022-08-11T08:08:39.000
dc.date.accessioned2022-08-23T16:03:15Z
dc.date.available2022-08-23T16:03:15Z
dc.date.issued1996-04-26
dc.date.submitted2006-09-14
dc.identifier.doi10.13028/2da8-1z95
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31439
dc.description.abstractThis thesis investigates the role of B cells as antigen-specific antigen-presenting cells (APC) in self tolerance to low concentrations of soluble self proteins and in acquired tolerance to low doses of soluble foreign protein antigens. Experiments were performed in normal and B cell-deficient animals, and tolerance induction was measured by T cell proliferation assays. T cell proliferation was reduced in B cell-deficient mice, indicating that B cells may be involved in efficient activation of naive T cells in response to protein antigen both in vivo and in vitro. To study acquired tolerance induced by low doses of soluble foreign protein antigen, normal and B cell-deficient adult mice were injected intravenously with repeated low doses (10 μg) of deaggregated ovalbumin (OVA), and then challenged with OVA in complete Freund's adjuvant. In animals treated with deaggregated OVA, the in vitro proliferative responses of LN T cells to OVA were significantly reduced, and production of the Th1 cytokine, IFN-γ, in response to OVA was lost. This occurred in both normal and B cell-deficient treated animals, indicating that B cell antigen presentation was not required for this phenomenon. B cells were also unnecessary for self tolerance of T cells to the transgenic self antigen, hen egg lysozyme (HEL), in a transgenic mouse strain with very low serum lysozyme concentration. Partial low zone tolerance induced by deaggregated, low-dose OVA was selective for the Th1 response, as measured by in vitro proliferation and IL-2 and IFN-γ production, because antibody responses of normal mice to this T cell-dependent antigen were largely unaffected. Both treated and untreated animals produced equivalent titers of anti-OVA antibodies, predominantly of the IgG1 and IgG2b isotypes, following challenge with OVA in complete Freund's adjuvant. Tolerance to low levels of the transgenic HEL self protein in mice expressing different MHC molecules was also addressed. Transgenic mice that were H-2b/b in the class II region were not tolerant to the transgenic self protein, whereas transgenic mice of the H-2b/k were tolerant.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectAntigen-Presenting Cells
dc.subjectB-Lymphocytes
dc.subjectImmunity
dc.subjectCellular
dc.subjectMice
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectAnimal Experimentation and Research
dc.subjectBiological Factors
dc.subjectCells
dc.subjectHemic and Immune Systems
dc.titleAnalysis of Low Zone Tolerance in Normal and B Cell-Deficient Mice
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1143&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/142
dc.legacy.embargo2017-04-24T00:00:00-07:00
dc.identifier.contextkey205333
refterms.dateFOA2022-08-25T04:01:33Z
html.description.abstract<p>This thesis investigates the role of B cells as antigen-specific antigen-presenting cells (APC) in self tolerance to low concentrations of soluble self proteins and in acquired tolerance to low doses of soluble foreign protein antigens. Experiments were performed in normal and B cell-deficient animals, and tolerance induction was measured by T cell proliferation assays. T cell proliferation was reduced in B cell-deficient mice, indicating that B cells may be involved in efficient activation of naive T cells in response to protein antigen both <em>in vivo</em> and <em>in vitro</em>. To study acquired tolerance induced by low doses of soluble foreign protein antigen, normal and B cell-deficient adult mice were injected intravenously with repeated low doses (10 μg) of deaggregated ovalbumin (OVA), and then challenged with OVA in complete Freund's adjuvant. In animals treated with deaggregated OVA, the <em>in vitro</em> proliferative responses of LN T cells to OVA were significantly reduced, and production of the Th1 cytokine, IFN-γ, in response to OVA was lost. This occurred in both normal and B cell-deficient treated animals, indicating that B cell antigen presentation was not required for this phenomenon. B cells were also unnecessary for self tolerance of T cells to the transgenic self antigen, hen egg lysozyme (HEL), in a transgenic mouse strain with very low serum lysozyme concentration. Partial low zone tolerance induced by deaggregated, low-dose OVA was selective for the Th1 response, as measured by <em>in vitro</em> proliferation and IL-2 and IFN-γ production, because antibody responses of normal mice to this T cell-dependent antigen were largely unaffected. Both treated and untreated animals produced equivalent titers of anti-OVA antibodies, predominantly of the IgG1 and IgG2b isotypes, following challenge with OVA in complete Freund's adjuvant. Tolerance to low levels of the transgenic HEL self protein in mice expressing different MHC molecules was also addressed. Transgenic mice that were H-2<sup>b/b</sup> in the class II region were not tolerant to the transgenic self protein, whereas transgenic mice of the H-2<sup>b/k</sup> were tolerant.</p>
dc.identifier.submissionpathgsbs_diss/142
dc.contributor.departmentMolecular Genetics and Microbiology
dc.description.thesisprogramImmunology and Microbiology


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