Dr. rer. nat. Henrik Mei
Deutsches Rheuma-Forschungszentrum Berlin
Ein Institut der Leibniz Gemeinschaft
Charitéplatz 1
10117 Berlin
Tel. +49 (0) 30 28460 774
mei@drfz.de
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 4505 25241
thomas.doerner@charite.de
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.
Ostendorf, L., Burns, M., Durek, P., Heinz, G.A., Heinrich, F., Garantziotis, P., Enghard, P., Richter, U., Biesen, R., Schneider, U., Knebel, F., Burmester, G., Radbruch, A., Mei, H.E., Mashreghi, M.F., Hiepe, F., Alexander, T. (2020). Targeting CD38 with Daratumumab in refractory Systemic Lupus Erythematosus. N. Eng. J. Med. 383, 1149-1155
Maity, P.C., Bilal, M., …Mei, H.E.,…Jumaa, H. (2020). IGLV3-21*01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling. Proc. Natl. Acad. Sci. USA 117, 4320-4327.
Chang, H.D., Tokoyoda, K., Hoyer, B., Alexander, T., Khodadadi, L., Mei, H., Dörner, T., Hiepe, F., Burmester, G.R., and Radbruch, A. (2019). Pathogenic memory plasma cells in autoimmunity. Curr. Opin. Immunol. 61, 86-91.
Cossarizza, A., Chang, H.D., Dörner, T.,…, Mei, H.E. … et al. (2019). Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur. J. Immunol. 49, 1457-1973.
Schett, G., Bozec, A., Bekeredjian-Ding, I., Chang, H.D., Dörner, T., Grassel, S., ..., Mei, H., Mielenz, D., ... Radbruch, A, et al. (2018). [New insights into the function of bone marrow]. Z. Rheumatol. 77, 4-7.
Baumgart, S., Schulz, A.R., Peddinghaus, A., Stanislawiak, S., Gillert, S., Hirseland, H., Krauthauser, S., Dose, C., Mei, H.E.*, and Grützkau, 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. 47, 1377-1385. *co-senior authors
Mei, H.E., Hahne, S., Redlin, A., Hoyer, B.F., Wu, K., Baganz, L., Lisney, A.R., Alexander, T., Rudolph, B., and Dörner, T. (2017). Plasmablasts With a Mucosal Phenotype Contribute to Plasmacytosis in Systemic Lupus Erythematosus. Arthritis Rheumatol. 69, 2018-2028.
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.
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.