The regulation of B lymphocyte proliferation via the antigen receptor will be studied with the eventual goal of understanding the molecular mechanisms of signalling and of growth control. Mature B cells are activated by contact with antigen to proliferate as part of the immune response resulting in production of specific antibody. Immature B cells, on the other hand, are inactivated by contact with antigen; a mechanism that can explain certain aspects of B cell tolerance. The growth of the immature B lymphoma cell line WEHI-231 is completely inhibited by anti-Ig (a surrogate for antigen) analogous to the response of normal immature B cells. This phenomenon will be studied with genetic and molecular genetic approaches. Mutants of WEHI-231 that are not inhibited by anti-Ig have been isolated and many more will be isolated. These mutants will be analyzed by genetic complementation to define genes and to determine dominance. Mutant phenotypes will be characterized by analyzing mIgM receptor numbers, capping, cell size changes in response to anti-Mu and intracellular Ca++ levels. Several schemes are proposed for recombinant DNA cloning of mutant genes. The cloning of these genes will allow numerous studies that should shed light on the role of these genes and their protein products in signalling or in growth control. Growth promoting components active in WEHI-231 may play a crucial role in the growth inhibition mechanism. These components will be studied by .nalyzing mRNA from WEHI-231 for the presence of known oncogenes, genes implicated in growth regulation by their ability to cause cancerous growth of cells.
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