B LYMPHOCYTES, IMMUNOLOGIC MEMORY, CELLULAR IMMUNITY, TRANSGENIC ANIMAL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。免疫系统提供对病毒、细菌等传染性病原体的保护，也对癌细胞提供保护。病原体被称为B和T淋巴细胞的特殊免疫细胞识别和消除。淋巴细胞不仅可以清除病原体，然后可以对过去积存的病原体做出更强的活力反应。这种增强的反应性被称为免疫记忆，可由自然感染(如水痘)或故意免疫(腮腺炎、麻疹、白喉、破伤风等)引起。免疫记忆存在的事实已经被认识了2000多年，然而我们对这一现象的了解一直很有限，主要是因为记忆淋巴细胞不能被明确地识别并因此被研究。迫切需要更好地了解免疫记忆，因为所获得的知识可以用来设计更好的疫苗，提供对病原体和癌细胞的保护性免疫。研究免疫记忆一直很困难，因为记忆淋巴细胞由于其表面缺乏特定的标记而不能被客观地识别。这项建议的目的是进一步发展一种基因工程小鼠模型，在该模型中，记忆B淋巴细胞被标记？细菌酶，β-半乳糖苷酶。现在，我们第一次可以直接研究记忆B细胞，我们将使用这个模型来回答关于B细胞记忆的基本问题。这项工作意义重大，因为完成后，我们将对记忆B淋巴细胞的发育、持久性和功能有更好的了解。这些知识将为设计开发有效疫苗的策略提供关键的见解，这些疫苗可以保护宿主免受癌细胞的攻击。

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. The immune system provides protection against infectious pathogens such as viruses, and bacteria and also against cancerous cells. Pathogens are recognized and eliminated by specialized immune cells known as B and T lymphocytes. Not only can lymphocytes eliminate pathogens, then can respond with enhanced vigor to pathogens enountered in the past. This enhanced responsiveness is called immunological memory and it can be elicited either by natural infection (as in the case of chickenpox) or by deliberate immunization (mumps, measles, diptheria, tetanus etc). The fact that immunological memory exists has been recognized for over 2000 years, yet our understanding of this phenomemon has been limited primarily because memory lymphocytes cannot be unambigously identified and hence studied. There is a pressing need to better understand immunological memory because the knowledge gained can be used to design better vaccines that provide protective immunity against pathogens and cancerous cells. Studying immune memory has been difficult because memory lymphocytes cannot be unambiquosly identified because they lack specific markers on their surface. The objective of this proposal is to further develop a genetically engineered mouse model in which memory B lymphocytes are ?tagged? with the bacterial enzyme, beta galactosidase. We can now, for the first time, study memory B cell directly and we will use this model to answer fundamental questions about B cell memory. The proposed work is significant, because upon completion, we will have a better understanding of the development, persistence, and function of memory B lymphocytes. This knowledge will provide critical insights into designing strategies to develop efficient vaccines that can protect the host against cancerous cells.