The long-term objectives of this proposal are directed towards defining the membrane lipid requirements of B and T lymphocytes.
The specific aims are: 1) To examine the uptake and utilization of exogenously-derived free fatty acids of B and T lymphocytes. Purified B and T cells will be incubated with isotopically-labeled fatty acids in vitro, and the capacities of the two cell types to incorporate the exogenous supplements into membrane lipids and fatty acid-linked proteins will be determined. 2) To determine whether increased levels of polyunsaturated fatty acids in T and B cell membranes affect lymphocyte-mediated functions. Two methods will be used to obtain T and B lymphocytes enriched with polyunsaturated fatty acids; in vitro incubation of purified T and B cells with linoleic acid, and isolation of T and B cells from mice fed a diet containing 20% corn oil. The linoleate-enriched lymphocytes will be assayed for their ability to display several immune functions in vitro and in vivo. 3) To identify the mechanisms by which saturated free fatty acids modulate in vitro antibody responses to T-dependent antigens. Splenic lymphocytes will be incubated in the presence of free fatty acids in vitro, and the effects of the lipids on T-helper versus T-suppressor cells will be examined. The experimental approaches used will combine membrane lipid chemistry with immunological techniques. This approach should provide valuable information regarding membrane lipids and immunocompetence, lipid metabolism during lymphocyte activation, and the relationship between high fat diets and immunosuppression.
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