STRUCTURE/FUNCTION HUMAN B CELL DIFFERENTIATION ANTIGENS

这项研究提案的主要目标是调查如何 人B细胞的增殖和分化受到调控。 主要焦点将放在细胞表面发生的相互作用上。 涉及B细胞分化抗原。我们的方法源于 从我们的发现来看，某些单抗(MAb) 某些B细胞相关抗原上的表位具有激动性 活性：单抗1F5与35kD PAN B细胞标志物Bp35 激活静息B细胞离开G0，进入G1期 细胞周期。相反，单抗G28-5对50Kd的PAN B细胞 抗原BP50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。我们的理论基础是激动型单抗 提供替代和补充的解决方案 研究B细胞免疫调节的因素。我们目前的情况 假设Bp35和Bp50是任何一种的表面受体 可溶性B细胞刺激因子(BSF)或跨膜 辅助细胞发出的细胞-细胞相互作用信号。具体的 该提案的目的是：1)测试BP35或BP50是否 已知的可溶性BSF的受体，2)评估其影响 抗Bp35和抗BP50激动型单抗对生长因子的影响 调节，3)表征和对比细胞内 激动型单抗在B细胞中诱导的途径，以及4) Bp35表面编码基因的克隆与分离 多肽。关于Bp35和BP50结构的更多信息 它们在B细胞激活中的作用将有助于我们的 对淋巴组织的病因和可能的控制的认识 恶性肿瘤和抗体介导的自身免疫性疾病。

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.