B LYMPHOCYTES, IMMUNOLOGIC MEMORY, CELLULAR IMMUNITY, TRANSGENIC ANIMAL

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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.