B CELL MEMORY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 免疫记忆或对召回抗原的夸大免疫反应是由记忆B和T淋巴细胞介导的，它们在抗原攻击解决后长期存在于宿主体内。B细胞存储器的存在已被公认为 然而，我们对这种现象的了解是有限的，主要是因为记忆B细胞缺乏特定的、永久的细胞表面标记，因此无法明确地识别它们。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，永久地标记和识别记忆B细胞。在这个模型系统中，cre介导的重组诱导生发中心B细胞及其直系后代记忆B细胞中b-半乳糖苷酶的永久表达。 本申请的目的是验证这一小鼠模型系统，并回答有关记忆B细胞定位和分化程序的基本问题。利用这个模型，我们对二次抗体反应进行了详细的分析。我们观察到，与公认的教条相反，当动物两次暴露于同一抗原时，出现的大规模次级反应并不是由于记忆B细胞克隆的优先扩张。 我们发现，三分之一的记忆反应是由分化为浆细胞的记忆B细胞组成的，而三分之二的记忆反应是由NA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。

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.