STRUCTURE/FUNCTION HUMAN B CELL DIFFERENTIATION ANTIGENS

结构/功能人 B 细胞分化抗原

• 批准号: 3293713
• 负责人: Edward A Clark
• 金额: $ 9.7万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3293713
• 关键词: B lymphocyte; cell cell interaction; cell differentiation; cell growth regulation; cell population study; chemical structure function; cytogenetics; growth factor; immunoregulation; leukocyte activation /transformation; molecular cloning; monoclonal antibody; monokines; surface antigens

The principal goal of this research proposal is to investigate how proliferation and differentiation of human B cells are regulated. A major focus will be on interactions occurring at the cell surface that involve B cell differentiation antigens. Our approach stems from our findings that monoclonal antibodies (mAb) to certain epitopes on certain B cell-associated antigens have agonistic activity: the mAb 1F5 to the 35Kd pan B cell marker Bp35 activates resting B cells to leave G0 and enter the G1 phase of the cell cycle. In contrast, the mAb G28-5 to the 50Kd pan B cell antigen Bp50 does not affect resting B cells, but like certain B cell growth factors (BCGF), stimulates activated B cells to traverse the cell cycle. Our rationale is that agonistic mAb provide an alternative and complementary approach to soluble factors for studying B cell immunoregulation. Our current hypothesis is that Bp35 and Bp50 are surface receptors for either soluble B cell stimulating factors (BSF) or for transmembrane cell-cell interaction signals from accessory cells. The specific aims of the proposal are: 1) to test whether Bp35 or Bp50 are receptors for known soluble BSF, 2) to assess the effects that anti-Bp35 and anti-Bp50 agonistic mAb have on growth factor regulation, 3) to characterize and contrast the intracellular pathways that are induced in B cells by agonistic mAb, and 4) to clone and isolate the gene which encodes for the Bp35 surface polypeptide. Further information about Bp35 and Bp50 structure and their role in B cell activation will contribute to our understanding of the etiology and possible control of lymphoid malignancies and antibody-mediated autoimmune diseases.

本研究的主要目的是探讨如何 调节人B细胞的增殖和分化。 一个主要的重点将是在细胞表面发生的相互作用 涉及B细胞分化抗原。 我们的方法源于 从我们的发现，单克隆抗体（mAb），以某些 某些B细胞相关抗原上的表位具有激动性 活性：mAb 1F 5对35 Kd pan B细胞标记物Bp 35 激活静息B细胞，使其离开G 0期，进入G1期， 细胞周期 与此相反，mAb G28-5对50 Kd pan B细胞的杀伤作用 抗原Bp 50不影响静息B细胞，但像某些B细胞一样 细胞生长因子（BCGF），刺激活化的B细胞， 遍历细胞周期。 我们的理论是， 提供了一种替代和补充的方法， 研究B细胞免疫调节的因素。 我们目前 假设Bp 35和Bp 50是 可溶性B细胞刺激因子（BSF）或用于跨膜 来自辅助细胞的细胞间相互作用信号。 具体 该提案的目的是：1）测试Bp 35或Bp 50是否 已知可溶性BSF的受体，2）评估 抗-Bp 35和抗-Bp 50激动性mAb对生长因子 调控，3）表征和对比细胞内 通过激动性mAb在B细胞中诱导的途径，和4） 克隆并分离编码Bp 35表面的基因 多肽。 关于Bp 35和Bp 50结构的更多信息 它们在B细胞活化中的作用将有助于我们 了解淋巴结炎的病因和可能的控制 恶性肿瘤和抗体介导的自身免疫性疾病。