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oai:www.ideals.illinois.edu:2142/71169 2023-07-11 col_2142_5131 col_2142_16338 com_2142_5130 com_2142_16337 com_2142_14793 com_2142_8903

Ballard, Dean Williams 2014-12-16T06:12:54Z 2014-12-16T06:12:54Z 10000-01-01 1985 1985 New Zealand BW mice spontaneously develop lymphocytic disorders and express autoantibodies in association with an autoimmune disease similar to human SLE. A comparative monoclonal analysis of spontaneous and experimentally-induced antibody responses in autoimmune BW mice was facilitated by hybridoma technology. Various immunochemical and physicochemical parameters of generated monoclonal antibodies were examined to provide a qualitative functional and structural description of such etiologically distinct antibody repertoires in the context of inherent cellular and humoral abnormalities characteristic of this strain. Ten monoclonal anti-DNA autoantibodies, derived from nonmanipulated BW mice and specific for various forms of DNA, were found to contain either IgG2a or IgG2b heavy chains related by a cross-reactive allotypic determinant. Binding studies, which employed defined DNA restriction fragments and synthetic nucleic acids, indicated that: (1) both helical conformation and nucleotide composition were involved in antibody recognition of duplex and single-stranded DNA, and (2) anti-DNA antibodies formed stable complexes with short synthetic oligonucleotides (<15 bases). Serological analyses of the expression of distinct idiotypic determinants possessed by purine and pyrimidine specific antibodies indicated the potential for an extensive clonal repertoire. Thirty-eight monoclonal anti-fluorescein antibodies were derived from immunized BW mice to evaluate various aspects of induced antibody expression, including isotype and affinity distribution. Monoclonal IgM antibody 18-2-3, produced from an initial BW cell fusion, exhibited low-temperature insolubility and an unusually high hapten-binding affinity (K(,A)) of 2.9 x 10('10) M('-1). Insolubility at low temperature was reversible in the presence of fluorescyl ligand, indicative of active site involvement in the mechanism of 18-2-3 cryoprecipitation. All other IgM and IgG proteins were restricted in hapten-binding affinities (K(,A) < 7 x 10('7) M('-1)) and possessed normal solubility properties, suggesting that 18-2-3 was derived from a relatively rare B cell progenitor. Relative subclass frequencies for 30 monoclonal IgG proteins were consistent with those reported for polyclonal thymic-dependent responses in normal strains, thus providing no evidence that T cells involved in regulation of IgG subclass expression are compromised in autoimmune BW mice. Made available in DSpace on 2014-12-16T06:12:54Z (GMT). No. of bitstreams: 1 8511577.pdf: 8746489 bytes, checksum: bb354416bd08ba27b4f6e54a6d28a793 (MD5) Previous issue date: 1985 Embargo set by: Seth Robbins for item 71335 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs U of I Only 290 p. Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1985. http://hdl.handle.net/2142/71169 (UMI)AAI8511577 Health Sciences, Immunology Monoclonal Analysis of Spontaneous and Induced Antibody Responses in Autoimmune New Zealand Mice text Microbiology Microbiology University of Illinois at Urbana-Champaign Dissertation Ph.D.