GERMINAL CENTER INTERACTIONS OF NORMAL/MALIGNANT B CELLS

滤泡性淋巴瘤是不治之症。从形态上看，它们 概述了继发性骨肉瘤正常生发中心的结构。 淋巴滤泡。滤泡性淋巴瘤常见的独特成分和 正常的生发中心是滤泡树突状细胞(FDC)。FDC是 生发中心微环境中的主要支持细胞 B细胞正常分化。假设FDDC对以下各项至关重要 调节正常B细胞的生长和分化为记忆或 抗体分泌细胞。B细胞与FDCs的相互作用是介导性的 VLA-4主要通过黏附受体参与B细胞信号传导 通过激活酪氨酸激酶通路来激活细胞。最近的证据 提示整合素介导的信号转导对细胞的生长和 正常和恶性细胞的存活，这可能对控制很重要 程序性细胞死亡。在这方面要研究的一个中心假设 有人提出，β1整合素介导的信号转导从根本上说是 对调节B细胞的生长和存活很重要。用胶合体 淋巴瘤中，FDCs与肿瘤B细胞的黏附作用是 完好无损，并使用相同的受体-配体对。目前，有 对疾病控制中心对正常的影响的性质的认识有限 B细胞以及FDCs是否可以影响恶性B细胞的生长。这个 这个项目的主要目标是研究Normal 伴有FDCs的肿瘤性B细胞。为此，我们计划开展四项工作 明确的目标。首次研究Beta1整合素介导的信号转导 酪氨酸磷酸化对正常和恶性B细胞的影响 蛋白质。二是优化体外扩增条件 FDC的维护和维护。第三，检查疾病控制中心的影响 对正常B细胞生长存活的影响及信号识别 它们会调节这些影响。第四，研究金融中心对经济发展的影响 滤泡性淋巴瘤细胞的生长和存活。对这一概念的理解 FDC和FDC之间可能发生的细胞间相互作用和信号转导 滤泡性淋巴瘤细胞可能为未来的治疗策略提供 来调节这些肿瘤的生长。

Follicular lymphomas are incurable diseases. Morphologically, they recapitulate the architecture of normal germinal centers of secondary lymphoid follicles. A unique component common to follicular lymphomas and normal germinal centers is the follicular dendritic cell (FDC). FDCs are athe major supporting cell in the germinal center microenvironment in which B cells normally differentiate. FDCs are hypothesized to be essential to the regulation of normal B cell growth and differentiation into memory or antibody secreting cells. The interaction of B cells with FDCs is mediated principally by the adhesion receptor VLA -4 is involved in signaling to B cells through activation of the tyrosine kinase pathway. Recent evidence suggests that integrin mediated signaling is critical to the growth and survival of normal and malignant cells, and may be important to the control of programmed cell death. A central hypothesis to be investigated in this proposal is that beta1 integrin mediated signaling is fundamentally important to the regulation of B cell growth and survival. In collicular lymphomas, the adhesive interaction of FDCs with neoplastic B cells is intact and employs the same receptor-ligand pair. Presently, there is limited understanding of the nature of the influences of FDCs upon normal B cells and whether FDCs they can affect malignant B cell growth . The primary goal of this project is to investigate the interactions of normal and neoplastic B cells with FDCs. To this end we plan to undertake four Specific Aims. First to investigate beta1 integrin mediated signaling in normal and malignant B cells through studies of tyrosine phosphorylated proteins. Second to optimize the in vitro conditions for expansion and maintenance and maintenance of FDCs. Third to examine the effects of FDCs on the growth and survival of normal B cells and to identify the signals which mediate those effects. Fourth to examine the effects of FDCs on the growth and survival of follicular lymphoma cells. An understanding of the cell-cell interactions and signaling which may occur between FDCs and follicular lymphoma cells may provide future therapeutic strategies with which to modulate the growth of these tumors.