B CELL MEMORY

B细胞记忆

• 批准号: 7958268
• 负责人: JOSHY JACOB
• 金额: $ 5.67万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958268
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Antibody Formation; Antigens; B-Lymphocytes; Biological Models; Cell surface; Communicable Diseases; Computer Retrieval of Information on Scientific Projects Database; Funding; Galactosidase; Genetic Recombination; Grant; Immune; Immune response; Institution; Mediating; Memory; Memory B-Lymphocyte; Modeling; Plasma Cells; Primates; Research; Research Personnel; Resolution; Resources; Source; Structure of germinal center of lymph node; T-Lymphocyte; Time; Transgenic Mice; United States National Institutes of Health; design; mouse model; programs; response

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. Immune memory or the exaggerated immune response to recall antigens is mediated by memory B and T lymphocytes that persist in the host long after resolution of the antigenic insult. The existence of B cell memory has been recognized for a long time, yet our understanding of this phenomenon is limited primarily because memory B cells cannot be unambiguously identified as they lack specific, permanent cell surface markers. To bridge this gap, we have designed and created a transgenic mouse model system to permanently "mark" and identify memory B cells. In this model system cre-mediated recombination induces permanent expression of b-galactosidase in germinal center B cells and their lineally descendant memory B cells. The objective of this application is to validate this mouse model system and to answer fundamental questions about the localization and differentiation program of memory B cells. Using this model we have dissected in detail the secondary antibody responses. We observed that contrary to the accepted dogma, the massive secondary response seen in animals when exposed to the same antigen twice is not due to a preferential expansion of memory B cell clones. We showed that one third of the memory response is comprised of memory B cells differentiating into plasma cells while two thirds are comprised of rapid expansion of na¿ve antigen-specific B cells. Understanding B-cell memory response will facilitate our understanding of infectious diseases such as AIDS.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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 研究中心，而研究中心不一定是研究者所在的机构。 免疫记忆或对回忆抗原的过度免疫应答是由记忆B和T淋巴细胞介导的，这些淋巴细胞在抗原损伤消退后很长时间内仍存在于宿主体内。B细胞记忆的存在已被公认为 很长一段时间以来，我们对这一现象的理解是有限的，主要是因为记忆B细胞不能被明确地识别，因为它们缺乏特异性的、永久性的细胞表面标记。为了弥补这一差距，我们设计并创建了一种转基因小鼠模型系统来永久“标记”和识别记忆B细胞。在该模型系统中，cre介导的重组诱导在生发中心B细胞和其直系后代记忆B细胞中永久表达β-半乳糖苷酶。 本申请的目的是验证这种小鼠模型系统，并回答有关记忆B细胞的定位和分化程序的基本问题。使用该模型，我们详细剖析了二次抗体反应。我们观察到，与公认的教条相反，当暴露于相同抗原两次时，在动物中观察到的大量次级应答不是由于记忆B细胞克隆的优先扩增。 我们发现，记忆反应的三分之一是由记忆B细胞分化成浆细胞组成的，而三分之二是由幼稚抗原特异性B细胞的快速扩增组成的。 了解B细胞的记忆反应将有助于我们了解艾滋病等传染病。