THE B-CELL BIOLOGY OF AGING

Scripps Research Institute, La Jolla CA

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Abstract

DESCRIPTION: This project concerns the changes in development, maturation, and tissue distribution of B cell subsets in the bone marrow and spleen of aged as compared to young mice. The project focuses upon two observations: increased longevity exhibited by B cells from aged mice and increased proportions and numbers of mature B cells within the bone marrow of aged mice. In Specific Aim 1, the longevity of defined B cell subsets in aged vs. young mice will be determined by labeling donor B cells with CFSE and assessing their turnover with time after adoptive transfer to non-irradiated young or aged recipients. This will enable a determination of the relative role of B cell intrinsic alterations vs. differences in the aged micro environment in the increased longevity seen in senescent B cells. Once the turnover of aged and young B cells is established in conventional recipients, mice with genetic alterations affecting B or T cell development will be employed as recipients to determine mechanisms which can influence B cell longevity. In Specific Aim 2, the accumulation of mature B cells within the bone marrow of aged mice and the capacity of these B cells to respond to antigenic stimulation will be probed. Particular emphasis will be placed on defining molecular mechanisms through which the aged micro environment may promote the increase in mature B cell numbers within the bone marrow.