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Working Group Neuroimmunological diseases

In the working group Neuroimmunologic Diseases, the research focus is B-cell immunology and the pathogenesis of inflammatory CNS diseases such as multiple sclerosis and NMOSD.

Team

Research

We focus on B cell immunology and the pathogenesis of inflammatory CNS diseases such as multiple sclerosis and NMOSD.

B cells constitute an integral part of the immune system in health and disease. In people with multiple sclerosis, B cells contribute significantly to pathogenesis, diagnostic features such as the famous oligoclonal bands, and are target for some of the most effective disease-modifying therapies currently available, like B cell depletion, but are also targeted by a4 integrin blockers, S1P receptor modulator and others. Of note, B cell functions extend far beyond production of immunoglobulins.

B-cell functions and their modulation by immunotherapeutic compounds - Immanuel Klinik Rüdersdorf bei Berlin - Neurologie - Forschung
Fig. 1: B-cell functions and their modulation by immunotherapeutic compounds. Krumbholz et al., Sem. Immunol. 2014.

While in a classical model of autoimmunity the immune system is the effector and the target organ is passively attacked by the immune system, we nowadays observe that the CNS actively takes part in the inflammatory process. For example, we demonstrated that the TNF superfamily member TNFSF13b (BAFF) is produced even in healthy brain parenchyma and upregulated to the level of secondary lymphatic organs in MS lesions. BAFF is a key cytokine for survival and differentiation of classical B cells, and controls the size of the B cell pool. In the case of MS lesions, especially astrocytes can produce great amounts of BAFF. Upon inflammatory stimulation, the amount of BAFF produced per astrocyte can even exceeded that per macrophage. Thereby astrocytes contribute to a B cell fostering environment in MS.

Selected Publications