B cell differentiation in the germinal center reaction and the resulting memory B cell compartment in humans
Final Report Abstract
The germinal center (GC) reaction is the central process of T cell dependent humoral immune responses and is essential for affinity maturation of antibodies and the generation of long-lived memory B cells and plasma cells. We performed a multimodal single cell analysis of isolated GC B cells from eight human tonsils to obtain a better understanding of B cell differentiation processes in the GC. We identified 48 distinct stages of B cell differentiation and assigned specific processes to them. Immunoglobulin (Ig) V region sequences of the single cells revealed the complexity of ongoing somatic hypermutation and selection in the GC. We also contributed to a general multimodal single cell analysis of a human tonsil cell atlas. A largescale analysis of the complexity of the human memory B cell compartment by immunoglobulin V gene sequencing from nine memory B cell subsets from apheresis products of healthy adult donors is currently underway. Bioinformatic studies addressed the value of unique molecular identifiers in high throughput sequencing, tested optimal ways to identify cell multiplets in single cell RNA-sequencing studies, and led to the establishment of an analysis pipeline for the evaluation of high throughput single cell IgV gene sequences.
Publications
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IgGeneUsage: differential gene usage in immune repertoires. Bioinformatics, 36(11), 3590-3591.
Kitanovski, Simo & Hoffmann, Daniel
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The life of B cells according to JEM. Journal of Experimental Medicine, 218(5).
Küppers, Ralf
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UMI or not UMI, that is the question for scRNA-seq zero-inflation. Nature Biotechnology, 39(2), 158-159.
Cao, Yingying; Kitanovski, Simo; Küppers, Ralf & Hoffmann, Daniel
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Human IgM–expressing memory B cells. Frontiers in Immunology, 14.
Budeus, Bettina; Kibler, Artur & Küppers, Ralf
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An atlas of cells in the human tonsil. Immunity, 57(2), 379-399.e18.
Massoni-Badosa, Ramon; Aguilar-Fernández, Sergio; Nieto, Juan C.; Soler-Vila, Paula; Elosua-Bayes, Marc; Marchese, Domenica; Kulis, Marta; Vilas-Zornoza, Amaia; Bühler, Marco Matteo; Rashmi, Sonal; Alsinet, Clara; Caratù, Ginevra; Moutinho, Catia; Ruiz, Sara; Lorden, Patricia; Lunazzi, Giulia; Colomer, Dolors; Frigola, Gerard; Blevins, Will ... & Heyn, Holger
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B Cell Differentiation and the Origin and Pathogenesis of Human B Cell Lymphomas. Methods in Molecular Biology, 1-30. Springer US.
Weniger, Marc A.; Seifert, Marc & Küppers, Ralf
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Single Cell VDJ Sequencing of Normal and Malignant B and T Cells. Methods in Molecular Biology, 295-346. Springer US.
Schnormeier, Ann-Kathrin & Budeus, Bettina
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Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion. Nature Cardiovascular Research, 3(5), 525-540.
Tuz, Ali A.; Ghosh, Susmita; Karsch, Laura; Ttoouli, Dimitris; Sata, Sai P.; Ulusoy, Özgür; Kraus, Andreas; Hoerenbaum, Nils; Wolf, Jan-Niklas; Lohmann, Sabrina; Zwirnlein, Franziska; Kaygusuz, Viola; Lakovic, Vivian; Tummes, Hannah-Lea; Beer, Alexander; Gallert, Markus; Thiebes, Stephanie; Qefalia, Altea; Cibir, Zülal ... & Singh, Vikramjeet
