Abstracts (complete list) - Wissenschaft Online

Katrin Moser, Oliver Winter, Nicole Haupt, Martin Szyska, Bimba F. Hoyer, Andreas
Radbruch, Falk Hiepe, Rudolf A. Manz
Plasma cell longevity in NZB/W mice
Through the production of autoantibodies, plasma cells contribute to the pathogenesis
of Systemic lupus erythematosus (SLE). In non-autoimmune individuals, long-term
plasma cell survival occurs mainly in the bone marrow where lifetime can reach several
months to years. The longevity of these cells depends on factors like IL-6 and SDF-1,
produced by accessory cells. In NZB/W mice, a model for SLE, high numbers of plasma
cells also survive in the spleen. We here address the question whether this abnormal
plasma cell survival in spleens of NZB/W mice is due to an increased potential of this
tissue to support plasma cell longevity and/or due to an enhanced intrinsic survival
capacity of NZB/W plasma cells. To analyse the intrinsic survival capacities of plasma
cells from different genetic backgrounds we performed in-vitro cultures with isolated
plasma cells. Without addition of survival factors nearly all plasma cells died within 3
days of culture. Addition of IL-6 resulted in an increase in surviving plasma cells which
was much more pronounced with plasma cells derived from autoimmune NZB/W and
NZB mice compared to plasma cells from non-autoimmune Bl6 and NZW mice.
However, plasma cells of BALB/c origin showed the same survival capacity as NZB/W
derived ones. Possibly indicating that higher sensitivity for IL-6 mediated survival can
contribute, but is not sufficient to explain the increased plasma cell survival in NZB/W
spleens. Therefore we also tested the microenvironment of plasma cells in the spleen of
NZB/W mice in tissue sections for the presence of increased production of plasma cell
survival factors. SDF-1 signals were found in close proximity to some, but not all
plasma cells. Increased numbers of a subset of myeloid related cells located in close
proximity to plasma cells and expressing multiple cytokines known to stimulate plasma
cell survival were detected in NZB/W spleens. This finding stresses a main impact of the
splenic microenvironment for the increased survival rate in NZB/W spleens.