Humorale Immunologie

Alumni seit 2009

Manz

Einleitung

This group was resident at the DRFZ from 2001 to 05/2009. Starting from 06/2009 the group moved to the University of Lübeck, Germany. In addition to its successful research program, the group established confocal microscopy at the DRFZ. This method allows to investigate cellular interaction in vivo, important to identify cellular contacts relevant for the regulation of immunological and inflammatory processes.

Currently, the former leader of the group is member of the Excellence Cluster “Inflammation at Interfaces”, Professor for “Immunology of Inflammation” and head of a research division at the Institute for Systemic Inflammation Research (ISEF) at the University of Lübeck, Germany.

The group focuses on the biology of B cells and plasma cells. Th rough the production of antibodies, these cells mediate specific immune protection, but also can contribute to the pathogenesis of many autoimmune (rheumatic) diseases.

During the last years we have shown that plasma cells can survive for months or years in environmental niches in the bone marrow or inflamed tissues. In autoimmune diseases like systemic lupus erythematosus (SLE), these long-lived plasma cells contribute to the production of persistent auto-antibody titers. Our work suggests that factors produced within their niches also protect long-lived plasma cells from the effects of conventional immunosuppressive therapies. Therefore, it is one of our main goals to characterize plasma cell niches in detail to identify components of these microcompartments that are suitable as therapeutic targets to suppress autoantibody production.

Current results from us and others show that additional cell types – hematopoietic lineage cells such as macrophages, dendritic cells, megakaryocytes and eosinophils – contribute to the function of plasma cell niches (Winter et al., 2010; Mohr et al., 2009; Belnoue et al., 2008; Chu et al., 2011). In addition to a stromal component, these hematopoietic cells represent a second component of plasma cell niches that is essential for their function. Importantly, this second component offers novel options to manipulate plasma cell niches and antibody responses. We were able to demonstrate that megakaryocytes contribute to at least 30% of plasma cell niches in the bone marrow and that injection of thrombopoietin – a megakaryocyte specific growth factor – boosts antibody responses because it allows newly formed plasma cells to home to the bone marrow and persist there in increased numbers (Winter et al., 2010). These results provide the proof-of principle that plasma cell niches represent a promising target to modulate plasma cell responses.

Another strategy to deplete pathogenic plasma cells and suppress autoantibodies is direct depletion of plasma cells by the proteasome inhibitor Bortezomib. Together with various collaborations partners we extended our earlier studies in this field to show that this treatment efficiently eliminates autoantibody production and suppresses autoimmune disease in ANCAinduced murine glomerulonephritis and experimental autoimmune myasthenia gravis.

Rudolf A. Manz

Prof. Dr. rer. nat. Rudolf A. Manz

Neue Adresse
Institut für Systemische
Entzündungsforschung
Ratzeburger Allee 160
23538 Lübeck
Germany

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