LIPID GROWTH FACTOR FOR NORMAL AND MALIGNANT B CELLS

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We have identified a lipo-protein complex with growth-promoting properties in supernates of human lymphoblastoid cell lines and activated normal B cells. The protein moiety is prealbumin which originates from the culture medium. Prealbumin (P) combines with a novel lipid factor (LF) that is synthesized and released by B cells to form LFP. According to mass spectrometric analysis, LF occurs in at least three forms. All contain long-chain, unsaturated fatty acids. The possible elemental composition of one LF form is C22 H43 ON. B cell produced LFP was discovered due to its ability to increase proliferation of B cells at low density which qualifies the lipid as an autocrine growth factor. A second broader range of effects has been identified in preliminary experiments. We propose a comprehensive study of the biochemistry, biology and immunobiology of LFP. We will isolate and analyze the different forms of LF by gas chromatography/mass spectrometry, NMR and IR (expecting to find different fatty acid moieties in a common derivative, such as perhaps a fatty acid amide), and we will attempt to synthesize LF. Using the synthetic LF preferentially, we will determine the physical properties of LFP and possible other LF-carrier complexes, will determine the physiology of LFP for normal and cloned B and T cells. We will begin the analysis of the role of LFP in the immune response, focusing on its place in the lymphokine cascade. Supported by evidence that lymphoma cell lines release as well as respond to LFP, we also propose to determine the significance of LFP in malignancy. Finally, we will perform studies on the mechanism of LFP action, beginning with LFP binding to a cellular receptor and the intracellular fate of LF.