| An important facet of long-lived immunity is the continuous synthesis of protective antibody provided primarily by long-lived bone marrow plasma cells. Despite its importance to maintain health, limited information exists on the mechanisms underlying long-lived plasma cell survival. My studies were designed to determine if stromal cells participate in plasma cell survival, whether plasma cells from different tissues are similar in their survival capacities, and whether immune tissues are alike in their ability to support plasma cell survival.; Plasmablasts, precursors of plasma cells, migrate from secondary lymphoid tissues and enter the bone marrow where they complete their differentiation into plasma cells. A critical element of the marrow microenvironment is the reticular stromal cell. I therefore tested the ability of bone marrow stromal cells to support plasma cell survival. The results show plasma cells survive up to four weeks in culture when stromal cells are present. In contrast, plasma cells cultured in the absence of stromal cells die rapidly. Additionally, I tested some of the factors that may regulate the lifespan of plasma cells. Binding of VLA-4 on plasma cells with its ligand is essential for plasma cells survival however VCAM-1 and CD44 are not. Moreover, stromal cell-derived IL-6 is needed to maintain antibody secretion and plasma cell viability.; I also compared the survival of long-lived bone marrow plasma cells with short-lived plasma cells of the spleen. Antibody levels are similar from splenic and bone marrow plasma cells and the majority of the plasma cells from the two tissues appear to die rapidly in culture. However, a small subpopulation of bone marrow plasma cells is maintained at least three weeks suggesting that a unique population of plasma cells exist in the bone marrow with an extended lifespan. Stromal cells isolated from the bone marrow, spleen, and lymph node are all capable of supporting plasma cell survival, however antibody levels are always greater when the stromal cell source is the marrow. Taken together, the data suggest plasma cell lifespan may be genetically programmed to some degree but is primarily influenced by the microenvironment of the different lymphoid tissues. |
