The research concerns the mechanisms of neoplastic transformation of B cells and their progression to form metastatic lymphomas. As a model system, we are studying avian lymphoid leukosis (LL), a common B cell neoplasm of chickens induced by slowly transforming RNA tumor viruses of the avian leukosis virus (ALV) group. Previous studies of LL, both in this and other laboratories, indicate that the natural history of the disease is characterized by a multi-stage process that is related to the maturation of the B lymphocyte.
Our aim i s to explore the relationship between cellular differentiation and maturation and the viral or oncogene controlled events of infection, transformation and metastasis. Specifically, we will i) Determine whether the capacity of the ALV to infect and replicate in lymphocytes is dependent on the state of differentiation or maturation of the B cell, and determine the basis of differential infection of bursal cells at the follicular level; ii) determine whether LL tumor progression and metastases are associated with immunosuppression related to expression of viral or MHC antigens; iii) determine whether virus-induced transformation of bursacytes occurs prior to or after V-C joining of immunoglobulin heavy or light chain; iv) determine whether resistance to tumor development in ALV-susceptible lines of chickens is related to a defect in viral replication; vi) examine the expression of the cellular oncogenes c-myc and Blym; during normal B cell maturation and at different stages of LL tumor progression; vii) analyze B cell maturation and early events in ALV and oncogene-induced transformation in a newly developed in vitro culture system.
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