NCI PHYSICIAN-INVESTIGATOR DEVELOPMENT AWARD PROGRAM

该项目的总体目标是对细胞的功能进行表征 活化的但不是静止的人B细胞表面抗原的表达 淋巴细胞。这些抗原是细胞表面极好的候选抗原。 控制B细胞激活、增殖和 差异化。这项建议将涉及对B细胞的详细分析 激活抗原要特别注意：1)刺激 诱导它们的表达，2)它们与其他B细胞抗原的关系 在静息和活化的B细胞上均有表达，3)它们与 与增殖有关的生长和分化因子 B细胞和免疫球蛋白分泌的刺激，以及4) 这些抗原在肿瘤B细胞上的表达及其可能的作用 在肿瘤B细胞增殖中的作用。要做到这一点，单克隆体 已知的和新的B细胞激活抗原的抗体将是 发展起来的，并被广泛描述的。这些抗原的表达 将与B细胞活化/增殖阶段和 区分，更重要的是，将尝试定义 这些抗原在功能上的重要性。最后，B细胞的表达 激活抗原将在B细胞白血病和淋巴瘤上进行检测。 这样做是为了确定是否存在关联 肿瘤B细胞上的抗原表达与两者的能力 在体外对激活/增殖的生理触发反应为 以及临床表现和病程。

The overall aim of this project is the functional characterization of cell surface antigens expressed on activated but not resting human B lymphocytes. These antigens are excellent candidates for cell surface structures which control B cell activation, proliferation, and differentiation. This proposal will involve a detailed analysis of B cell activation antigens with specific attention to: 1) the stimuli which induce their expression, 2) their relationship to other B cell antigens expressed on both resting and activated B cells, 3) their relationship to growth and differentiation factors which are involved in the proliferation of B cells and stimulation of immunoglobulin secretion, and 4) the expression of these antigens on neoplastic B cells, and their possible role in neoplastic B cell proliferation. To accomplish this, monoclonal antibodies to previously known and new B cell activation antigens will be developed, and extensively characterized. The expression of these antigens will be related to the stages of B cell activation/proliferation and differentiation, and more importantly an attempt will be made to define the functional importance of these antigens. Finally, the expression of B cell activation antigens will be examined on B cell leukemias and lymphomas. This will be done in order to determine whether there is a correlation between antigen expression on neoplastic B cells and both the ability to respond to physiologic triggers of activation/proliferation in vitro as well as the clinical presentation and course of disease.