Abstracts (complete list) - Wissenschaft Online

Sven Hartmann, Antje M. Wengner, Uta E. Hoepken, Peter K. Petrow, Uta Schurigt,
Rolf Braeuer, Martin Lipp
CXCR5- and CCR7-dependent lymphoid neo-genesis in a
chronic model of antigen-induced arthritis (AIA)
Rheumatoid arthritis (RA) is a common autoimmune disease affecting about 1% of the
adult population and is mainly characterized by chronic, polyarticular, synovial
inflammation, which can lead to long-term joint damage resulting in chronic pain and
disability. The molecular and cellular pathogenic mechanisms, which lead to RA and
maintain the chronicity of the disease, are still poorly understood. Characteristically for
RA is the infiltration into the synovial tissue by granulocytes and large numbers of
mononuclear cells, such as T and B lymphocytes, monocytes, neutrophils and
macrophages. We have developed a novel model of antigen-induced arthritis in mice
resembling the chronic phase of the human disease including frequent formation of
ectopic follicular structures, a hallmark of human RA. In our model formation of ectopic
follicles with segregated B and T cell areas can be regularly induced by intra-articular
injection of mBSA into the knee joints of pre-immunized C57BL/6 and BALB/c mice. In
CXCR5- and CCR7-deficient mice the formation and organization of these ectopic
structures are severely impaired in proving that both chemokine receptors play an
important role in lymphoid neo-organogenesis during chronic inflammatory conditions
as in RA. Remarkably, most follicles show topologically segregated T and B cell areas
with presence of CD8 and CD4 T cells, the formation of active germinal centers (GC)
and generation of antigen-specific CD138+ plasma cells. Moreover, formation of ectopic
follicles is entirely dependent on the presence of the chemokine receptors CXCR5 or
CCR7. Our results suggest that continuous inflammatory stimuli, e.g. by autoantigens,
are sufficient to induce lymphoid neo-organogenesis at extra-nodal sites, which in turn
allows local antigen-dependent interaction of memory/effector B and T lymphocytes
resulting in aberrant chronic autoreactive immune responses.