Molecular and functional analysis of human splenic marginal zone B cells
Final Report Abstract
The spleen is a critical secondary lymphoid organ, and its splenic marginal zone (sMZ) B cells play an essential role in immune responses to blood-borne pathogens. This project focussed on the molecular and functional analysis of sMZ B cells, with the aim of clarifying their developmental pathways and their functional role in human B cell responses, as well as their similarities and differences compared to murine sMZ B cells. The results obtained from this study led to two major publications and one review article – and contributed to 3 collaborative projects. The first publication shows how memory B cells (MBCs) in the peripheral blood are systematically archived in the spleen throughout life, and undergo clonal expansion, so that eventually large MBC clones dominate the immune landscape in older individuals. This clonal dominance contributes to immune aging, as smaller clones are gradually outcompeted. The study also demonstrates that splenic MBCs play a key role in maintaining long-term immunity by providing a reservoir of primed memory cells that are ready to respond rapidly to infections. These findings enhance our understanding of immune aging, memory B cell maintenance, and the pathogenesis of B cell lymphomas. The second study was based on the analysis of splenic biopsies from healthy donors aged 3 to 48 years and identified a major subpopulation of CD27-negative sMZ B cells. These cells exhibit low IGHV mutation rates in early life but acquire an average memory B-cell signature as individuals age. The study challenges the notion that the sMZ primarily contains naïve B cells in infants, showing instead that these cells are already antigen-experienced and capable of activation and proliferation from a young age. This finding contributes to our understanding of the immune system’s early development and the role of the spleen in the defence against blood-borne pathogens.
Publications
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Effects of a Multimerized Recombinant Autoantibody Against Amyloid-β. Neuroscience, 463, 355-369.
Albus, Alexandra; Kronimus, Yannick; Neumann, Sascha; Vidovic, Natascha; Frenzel, André; Kuhn, Philipp; Seifert, Marc; Ziehm, Tamar; van der Wurp, Hendrik & Dodel, Richard
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Systematic memory B cell archiving and random display shape the human splenic marginal zone throughout life. Journal of Experimental Medicine, 218(4).
Kibler, Artur; Budeus, Bettina; Homp, Ekaterina; Bronischewski, Kevin; Berg, Victoria; Sellmann, Ludger; Murke, Florian; Heinold, Andreas; Heinemann, Falko M.; Lindemann, Monika; Bekeredjian-Ding, Isabelle; Horn, Peter A.; Kirschning, Carsten J.; Küppers, Ralf & Seifert, Marc
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The Splenic Marginal Zone in Children Is Characterized by a Subpopulation of CD27-Negative, Lowly IGHV-Mutated B Cells. Frontiers in Immunology, 13.
Kibler, Artur; Budeus, Bettina; Küppers, Ralf & Seifert, Marc
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A single-cell multi-omic and spatial atlas of B-cell lymphomas reveals differentiation drives intratumor heterogeneity. openRxiv.
Fitzgerald, Donnacha; Roider, Tobias; Baertsch, Marc-Andrea; Kibler, Artur; Horlova, Anastasiia; Chung, Erin; Vöhringer, Harald; Mathioudaki, Anna; Budeus, Bettina; Passerini, Verena; Knoll, Mareike; Mammen, Johannes; Li, Linsha; Caillé, Léandra; Czernilofsky, Felix; Bruch, Peter-Martin; Liebers, Nora; Meyer-Bender, Matthias; Siebert, Reiner ... & Huber, Wolfgang
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Age-related changes of the human splenic marginal zone B cell compartment. Immunology Letters, 256-257, 59-65.
Kibler, Artur; Seifert, Marc & Budeus, Bettina
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The inhibitory receptor Siglec‐G controls the severity of chronic lymphocytic leukemia. EMBO reports, 24(8).
Röder, Bettina; Fahnenstiel, Hannah; Schäfer, Simon; Budeus, Bettina; Dampmann, Maria; Eichhorn, Melanie; Angermüller, Sieglinde; Brost, Claudia; Winkler, Thomas H.; Seifert, Marc & Nitschke, Lars
