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: 7381149
• 负责人: STEPHEN M JACKSON
• 金额: $ 4.01万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381149
• 关键词: CELLS; BEARING; IGVH4; 34+; BCRS

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NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。展示自身反应性B细胞受体（BCR）的B细胞通常被删除或无反应。人类B细胞的免疫球IG VH 4 -34基因片段的生产性重排通常被确定在自身免疫和淋巴瘤B细胞群体，但他们通常逃脱BCR诱导的克隆删除。所采用的具体存活机制仍不清楚，但已提出改变的BCR信号模式（阈值、持续时间、信号级联的持续）作为可能的候选者。CD 45是存在于淋巴细胞上的蛋白酪氨酸磷酸酶，并且当处于其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VH 4 -34+抗体也与⑶ 45交叉反应。在这里，我们假设VH 4 -34 Ab对表面CD 45的识别应该促进CD 45二聚化和失活。因此，正常的BCR信号传导特性应被改变，可能产生有利于自身免疫/肿瘤进展的发育/分化状态。