Analysis of differential functional capacity and origins of memory B-lymphocyte subsets

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Immunological memory is a defining feature of the adaptive immune response. Very recently it was shown in the laboratory of Dr. M. Shlomchik that memory B-lymphocytes are comprised of clear phenotypic subsets that can be identified by specific expression of the cell-surface markers CD80, PD-L2 and CD73. By using NP-specific murine memory B cell systems, which provide a large number of antigen-specific memory B cells after immunization, I will further characterize these newly described subsets in the proposed fellowship. Main objectives are to determine their origins and to test whether memory B cell subsets have differential functional capacity. Experiments will be performed to address whether type and degree of stimulation influences the subset type of memory B cells generated. Subsets will be purified to identify proliferative and differentiative capacity in vitro and in vivo. These subsets will be further dissected using gene expression profiling, RT-qPCR, and FACS, comparing the subsets to each other and to naïve cells in order to obtain insight into differential function. The delineation of such memory B cell subsets should provide important insight into how secondary B cell responses function.