Henrik Mei

Dr.rer. nat. Henrik Mei

Deutsches Rheuma-Forschungszentrum Berlin
Ein Institut der Leibniz Gemeinschaft
Charitéplatz 1
10117 Berlin  

Tel. +49 (0) 30 28460774
mei@drfz.de

Thomas Dörner

Prof. Dr. med. Thomas Dörner

Leiter Klinische Hämostaseologie
Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie
Charité - Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin

Tel. +49 (0)30 450 525 241
thomas.doerner@charite.de

Project summary:

Heterogeneity and imprinting of long-lived plasma cells  

Soluble antibodies are essential players in immune defence and autoimmune disorders.

The long-term persistence of antibody titers is regulatedatthelevelof specialized and highly differentiated B cells, the plasma cells, some of which – supported by extrinsic survival factors or by intrinsic regulation – can survive for a very long time. However, control of the plasma cell pool, and how antibody titers are thereby regulated, is still enigmatic.

Weobtainedevidenceofarelevantheterogeneityamonghumanlong-livedbone marrow-resident plasma cellsbycharacterizing subsets ofCD19-expressing andCD19-lacking plasma cells. OurdataimplythatCD19- plasma cellsconferlong-termstabilityofantibodylevels, andthatCD19+ plasma cellsaremoredynamicandundergoturnover, permittingtheadaptationofhumoralmemory.

The existence of different subsets of plasma cells lends to the idea that not all plasma cells are regulated in the same way, but that some subsets may underlie distinct regulatory principles.

This project addresses the diversity of plasma cells and the lifestyles of plasma cell subsets on the phenotypic and functional level to elucidate the underlying mechanisms that determine their diversification. We expect that improved knowledge of plasma cell homeostasis will provide innovative insight into this compartment and enable therapeutic manipulation of the plasma cell pool with regard to immunity and autoimmunity.

Heterogeneity and imprinting of long-lived plasma cells
Publications TP 24:

Baumgart, S., Schulz, A.R., Peddinghaus, A., Stanislawiak, S., Gillert, S., Hirseland, H., Krauthauser, S., Dose, C., Mei, H.E.*, and Grutzkau, A*. (2017). Dual-labelled antibodies for flow and mass cytometry: A new tool for cross-platform comparison and enrichment of target cells for mass cytometry. Eur J Immunol., 2017 Aug;47(8):1377-1385. doi: 10.1002/eji.201747031. Epub 2017 Jul 18. *co-senior authors

Fleischer, S.J., Daridon, C., Fleischer, V., Lipsky, P.E., and Dorner, T. (2016). Enhanced Tyrosine Phosphatase Activity Underlies Dysregulated B Cell Receptor Signaling and Promotes Survival of Human Lupus B Cells. Arthritis & Rheumatology 68, 1210-1221.

Fleischer, S.J., Giesecke, C., Mei, H.E., Lipsky, P.E., Daridon, C., and Dorner, T. (2014). Increased frequency of a unique spleen tyrosine kinase bright memory B cell population in systemic lupus erythematosus. Arthritis & Rheumatology 66, 3424-3435.

Mei, H.E., Frolich, D., Giesecke, C., Loddenkemper, C., Reiter, K., Schmidt, S., Feist, E., Daridon, C., Tony, H.P., Radbruch, A., et al. (2010). Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab. Blood 116, 5181-5190.

Mei, H.E., Hahne, S., Redlin, A., Hoyer, B.F., Wu, K., Baganz, L., Lisney, A.R., Alexander, T., Rudolph, B., and Dorner, T. (2017). Plasmablasts with a mucosal phenotype contribute to plasmacytosis in SLE. Arthritis & Rheumatology.

Mei, H.E., Schmidt, S., and Dorner, T. (2012). Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity. Arthritis Res Ther 14 Suppl 5, S1.

Mei, H.E., Wirries, I., Frolich, D., Brisslert, M., Giesecke, C., Grun, J.R., Alexander, T., Schmidt, S., Luda, K., Kuhl, A.A., et al. (2015). A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow. Blood 125, 1739-1748.

Mei, H.E., Yoshida, T., Sime, W., Hiepe, F., Thiele, K., Manz, R.A., Radbruch, A., and Dorner, T. (2009). Blood-borne human plasma cells in steady state are derived from mucosal immune responses. Blood 113, 2461-2469.

Yoshida, T.*, Mei, H.E.*, Dorner, T., Hiepe, F., Radbruch, A., Fillatreau, S.**, and Hoyer, B.F.** (2010). Memory B and memory plasma cells. Immunol Rev 237, 117-139., *co-first authors, **co-senior authors