Hauser lab

Immune Dynamics

If the immune system reacts to a stimulus, a dynamic interplay of different cells is  triggered. Circulating and tissue-resident immune cells, as well as tissue-specific non-hematopoietic cells initiate, maintain, coordinate and terminate an immune reaction. In order to develop novel therapeutic strategies, it is necessary to understand these dynamic cellular interactions on a molecular level.

Long-lived plasma cells produce antibodies and are important players of immunological memory. They protect the body from recurrent infections. In the course of certain autoimmune diseases, however, long-lived plasma cells can produce autoantibodies which are detrimental.

The survival of long-lived plasma cells depends on extrinsic signals. It is therefore necessary to analyse their composition in the spatial context of the surrounding tissue. We have developed a novel microscopy technology, which allows us to follow the dynamic processes in these niches deep in the bone marrow over extended time periods. We could show that the blood vessels surrounding the plasma cell niches are highly dynamic and change their localisation relative to plasma cells. We are now investigating to what extent these changes affect plasma cells and the composition of the niches. We are also using multiplexed histological analyses, which allows us to stain up to 80 markers on one single tissue section, in order to decipher the code of the plasma cell niches.

Plasma cells can also be found in high numbers in the gut mucosa, where they produce massive amounts of IgA. We could show that a fraction of those plasma cells can become long-lived. Niches for long-lived IgA+ plasma cells derived from mucosal immune responses are present within the intestinal lamina propria, but also within the bone marrow. We are investigating whether gut-derived plasma cells include autoreactive cells.

In addition to the physiological sites described above, plasma cells can survive in a number of other tissues under conditions of chronic inflammation. We could show that long-lived plasma cells can persist even in the central nervous system, a tissue void of immune cells in healthy individuals. Consequently, we are now investigating whether antibodies produced by those intracerebral plasma cells contribute to neuronal damage, for example in multiple sclerosis (MS).

Keywords
Multiphoton microscopy
Plasma cells
Confocal microscopy
Hhistocytometry
Chronic inflammation