Item – Theses Canada

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OCLC number
27382584
Author
Heeney, Jonathan Luke,1957-
Title
The immunopathogenesis of enzootic bovine lymphoma.
Degree
Ph. D. -- University of Guelph, 1989
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, 1991.
Description
3 microfiches.
Notes
University Microfilms order no. UMI00283643.
Includes bibliographical references.
Abstract
Bovine leukemia virus (BLV) is a horizontally transmitted, widespread retroviral infection associated with lymphoid tumors in adult cattle. A rapid field test for the identification of BLV-infected cattle was developed for screening purposes. The immune response upon which this test was based, was studied in experimentally BLV-infected pregnant Hereford cattle. Titers to BLV transiently dropped during the calving period, but remained detectable and continued to increase during the study period. Subtle changes in the humoral response in BLV-infected cattle were manifested primarily by decreased total serum IgM. Changes in the humoral response in infected cows indicated that BLV may have a direct effect on B-lymphocytes. Alternatively, it was proposed that other cell types may be affected involving regulation of the humoral immune response. BLV proviral infection was detected in monocytes and B-cells as determined by Southern blot analysis for provirus and immunocytochemistry for BLV antigens. Evidence of BLV p24 antigen expression in vivo was detected infrequently but was found in lymph nodes of some infected cattle in follicular center cells, marginal zone lymphocytes and occasionally in sinus histiocytes. To determine if alterations in the circulatory compartment of the humoral immune system are reflected in lymph node populations in BLV-infected animals, changes in the distribution of lymph node lymphocytes were assessed immunohistochemically with bovine lymphocyte specific monoclonal antibodies. Observed changes were suggestive of asynchrony in differentiation of follicular B-cells. Minimally affected lymph nodes from cattle with lymphoma had colonization of cortex by large neoplastic lymphocytes which exhibited a B-cell phenotype. Characterization of BLV-associated tumors by biochemical, morphological, immunological and molecular methods demonstrated that BLV provirus containing lymphomas were of the B-cell type and were of diffuse large (DL) or diffuse large cleaved (DLC) morphology with elevated levels of the B-lymphocyte marker 5$\sp\prime$-Nucleotidase (5$\sp\prime$NT). A 220 kD cell membrane antigen was demonstrated to be common and prominent in all, BLV-seropositive tumors examined. Further genotypic analysis for isotype switching and phenotypic analysis by immunohistochemistry for B-cell differentiation markers conclusively demonstrated that all enzootic bovine lymphomas examined were of the B-cell lineage with a mature phenotype. In conclusion, the critical genetic lesions resulting in lymphocyte transformation in BLV-infected cattle most likely occur at a specific stage of differentiation late in B-cell ontogeny and are manifested as transformed, isotypically variable descendents of mature B-cells.
ISBN
031562292X
9780315622920