B CELL MEMORY

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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. 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.