PROJECT SUMMARY The behavior of B cell memory in mice and humans is an active area of research with implications for traditional vaccine design and for the development of our engineered B cell vaccine (parent award). There is data in mice supporting the idea that memory B cells have a very limited ability to re-enter germinal centers. Alternatively, it has been shown that di?erent memory phenotypes exist with some showing a preference for germinal center re-entry. We hypothesize that memory behavior, similar to naive cell behavior, may also depend on immunogen a?inity, valency, and availability of T cell help. We will explore these ideas by generating various memory phenotypes using in vitro B cell activation and adoptive transfer to increase the frequency of antigen-specific memory in the B6 mouse model (which is normally very low). We will then vaccinate using antigens with defined a?inities and valency’s to see if these factors impact memory cell developmental fates. We would also like to immunize memory at di?erent times to see if changing memory B cell surface markers are associated with altered cell behaviors in response to vaccination.