B CELLS BEARING IGVH4-34+ BCRS: TARGET-SPECIFIC INFLUENCES ON B CELL ACTIVATION

携带 IGVH4-34 BCRS 的 B 细胞：对 B 细胞激活的靶标特异性影响

• 批准号: 7959383
• 负责人: STEPHEN M JACKSON
• 金额: $ 3.28万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959383
• 关键词: Antibodies; Antigen Receptors; Antigens; Autoimmune Process; B-Cell Activation; B-Lymphocytes; Clonal Deletion; Computer Retrieval of Information on Scientific Projects Database; Development; Dimerization; Funding; Genes; Grant; Human; Institution; Lymphocyte; Mentors; PTPRC gene; Pattern; Population; Property; Protein Tyrosine Phosphatase; Receptor Signaling; Receptors, Antigen, B-Cell; Research; Research Personnel; Resources; Science; Signal Transduction; Source; Surface; United States National Institutes of Health; autoreactive B cell; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. B cells that display autoreactive B cell receptors (BCR) are typically deleted or anergized. Human B cells that productively rearrange the Ig VH4-34 gene segment are commonly identified among autoimmune and lymphomagenic B cell populations, yet they routinely escape BCR-induced clonal deletion. Specific survival mechanism(s) employed remain unknown, however altered BCR signaling patterns (threshold, duration, perpetuation of signal cascade) have been proposed as likely candidates. CD45 is a protein tyrosine phosphatase present on lymphocytes, and is centrally involved in antigen receptor signaling when in its active, monomeric form. Interestingly, VH4-34+ antibody against self I/i-antigen is also crossreactive with CD45. Here, we hypothesize that recognition of surface CD45 by VH4-34 Ab should promote CD45 dimerization and inactivation. As a consequence, normal BCR signaling properties should be altered, potentially generating a developmental/differentiation state that is conducive to autoimmune/neoplastic progression.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 表现出自身反应性 B 细胞受体 (BCR) 的 B 细胞通常会被删除或失去活性。有效重排 Ig VH4-34 基因片段的人类 B 细胞通常在自身免疫性和淋巴瘤性 B 细胞群中被发现，但它们通常会逃避 BCR 诱导的克隆缺失。 采用的具体生存机制仍然未知，但改变的 BCR 信号传导模式（阈值、持续时间、信号级联的持续）已被提议作为可能的候选机制。 CD45 是一种存在于淋巴细胞上的蛋白质酪氨酸磷酸酶，当其处于活性单体形式时，主要参与抗原受体信号传导。 有趣的是，针对自身 I/i 抗原的 VH4-34+ 抗体也与 CD45 发生交叉反应。 在此，我们假设 VH4-34 Ab 对表面 CD45 的识别应促进 CD45 二聚化和失活。 因此，正常的 BCR 信号传导特性应该被改变，可能产生有利于自身免疫/肿瘤进展的发育/分化状态。