B LYMPHOCYTE PRODUCTION AND TURNOVER IN AGED MICE

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It is not known whether B lymphocyte production and turnover rates remain constant throughout life, since detailed studies have only been performed in neonates or young adults. Because production and turnover rates dictate the mature B cell pool s size, and events critical to both self tolerance and lymphoid homeostasis occur at each stage of B cell differentiation, a thorough understanding of age-related changes in these parameters is essential for intelligent interpretation of age- associated alterations in immune function. In these studies, we will define the production and turnover properties of each major B cell differentiative stage in aged, middle aged, and young mice. We will employ in vivo BrdU labeling and multi-color cytofluorimetry for these determinations. Further, our preliminary data suggest the pre-B cell pool s dynamics differ in aged mice, indicating that either fewer pro-B cells successfully transit to the Pre-B cell pool, or that less proliferation occurs within the pre-B cell pool. Therefore, we will probe these alternatives by performing cell cycle analysis on pre-B cells from aged mice; and determining the intrinsic apoptotic death rates among the pro- and pre-B cells of aged mice.