NCI PHYSICIAN-INVESTIGATOR DEVELOPMENT AWARD PROGRAM

该项目的总体目标是细胞的功能表征， 活化但非静息人B表面抗原 淋巴细胞 这些抗原是细胞表面抗原的极好候选者。 控制B细胞活化、增殖和 分化 该提案将涉及B细胞的详细分析， 激活抗原，特别注意：1）刺激， 诱导它们表达，2）它们与其它B细胞抗原的关系 在静息和活化的B细胞上表达，3）它们与 参与增殖的生长和分化因子 B细胞和刺激免疫球蛋白分泌，和4） 这些抗原在肿瘤性B细胞上的表达及其可能的作用 肿瘤性B细胞增殖。 为了实现这一点，单克隆 针对先前已知的和新的B细胞活化抗原的抗体将被 发展，并广泛的特点。 这些抗原的表达 将与B细胞活化/增殖的阶段相关， 差异化，更重要的是，将尝试定义 这些抗原的功能重要性。 最后，B细胞表达 将在B细胞白血病和淋巴瘤上检查活化抗原。 这样做是为了确定是否存在相关性 肿瘤性B细胞上的抗原表达与 对体外激活/增殖的生理触发作出反应， 以及疾病的临床表现和病程。

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.