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Abstracts (complete list) - Wissenschaft Online

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Oliver Winter, Katrin Moser, Nicole Haupt, Martin Szyska, Andreas Radbruch, Rudolf A.<br />

Manz<br />

PLASMA CELL SURVIVAL AND DEVELOPMENT IN THE BONE<br />

MARROW<br />

Plasma cells secrete antibodies which are a key factor for the adaptive immune defence.<br />

Bone marrow is the major site where long-lived plasma-cells reside. Survival of these<br />

cells in specific microenvironments (niche) depends on survival factors supplied by<br />

proximate cells, including APRIL, IL-6, TNF-a. SDF-1+ reticular stromal cells found in<br />

association with plasma cells are likely to contribute to this niche.<br />

To further characterize these niches, we immunized B6 and Balb/c mice with the<br />

antigen ovalbumin, sacrificed them at several time points during the immune response<br />

and tracked ovalbumin specific plasma cells via confocal microscopy. Stromal cells<br />

found in close association with plasma cells were considered to contribute potentially to<br />

niches. These cells were further characterised by flow cytometry.<br />

Plasma cells enter the bone marrow via the vascular niche. Here, they are found during<br />

the first days following their immigration into the bone marrow in contact with B78+<br />

cells of the endothelial linage, possibly including mature endothelial cells and endothelial<br />

precursor cells. These plasma cells also make contact to Gr1 high cells, likely<br />

resembling mature granulocytes emigrating from the bone marrow.<br />

Later, at about 7 days after entering the bone marrow, plasma cells are found more<br />

distant from B78+ cells. They now are localized adjacent to VCAM-1+ reticular stromal<br />

cells where they also specifically bind to a particular type of myeloid related cells that<br />

produce multiple important plasma cell survival factors, including Il-6, TNF-a and APRIL.<br />

Our data suggest that following immigration of plasma cells via the vascular niche, longterm<br />

plasma cell survival later is supported in a second niche. Here, VCAM+ reticular<br />

stromal cells seem to provide a meeting point for long-lived plasma cells with myeloid<br />

related cells that support plasma cell survival through the production of multiple<br />

important plasma cell survival signals.

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