LIPID GROWTH FACTOR FOR NORMAL AND MALIGNANT B CELLS

我们已经确定了一种脂蛋白复合物， 人淋巴母细胞样细胞系和活化的 正常的B细胞。 蛋白质部分是前白蛋白，其来源于 培养基。 前白蛋白（P）与一种新的脂质因子结合 (LF)由B细胞合成和释放形成LFP。 根据 对于质谱分析，LF至少以三种形式出现。 所有 含有长链不饱和脂肪酸。 可能的元素 一种LF形式的组成是C22 H43 ON。 由于其在低浓度下增加B细胞增殖的能力， 密度，其使脂质有资格作为自分泌生长因子。 一 第二个更广泛的影响范围已确定在初步 实验 我们建议全面研究生物化学， LFP的生物学和免疫生物学。 我们将分离并分析 通过气相色谱/质谱、NMR和IR分析不同形式的LF （期望在共同的衍生物中发现不同的脂肪酸部分， 例如脂肪酸酰胺），我们将尝试合成 LF。 优先使用合成LF，我们将确定物理 LFP和其他可能的LF载体复合物的性质，将决定 正常和克隆B和T细胞的LFP生理学。 我们将开始 分析LFP在免疫应答中的作用，重点是其 在淋巴因子级联中的位置。 有证据表明淋巴瘤 细胞系释放以及响应LFP，我们还建议， 确定LFP在恶性肿瘤中的意义。 最后我们将 对LFP的作用机制进行研究，从LFP开始， 与细胞受体的结合和LF的细胞内命运。

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.