The role of B lymphocytes in arterial thrombosis

• Applicants: Professor Dr. Huige Li; Professor Dr. Christoph Ralf Reinhardt
• Subject Area: Cardiology, Angiology ; Hematology, Oncology ; Pharmacology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559134895

Immune cells are key players in thrombogenesis. Neutrophils, for instance, are involved in both venous and arterial thrombosis. We have recently shown that B lymphocyte deficiency promotes venous thrombosis. However, so far there are no reports on the role of B cells in arterial thrombosis. The present research proposal aims to fill this knowledge gap. In the first part, we will study the role of B lymphocytes in arterial thrombosis by using two mouse models of B-cell deficiency, the genetically modified JHT mice with permanent B cell depletion, and wild-type mice with transient B cell depletion by anti-CD20 antibody treatment. In addition, adoptive B-cell transfer experiments will be performed to further validate the results. Based on our previous publications and preliminary data, we expect that B cell depletion leads to enhanced arterial thrombosis. In the second part of the project, we will address the underlying molecular mechanisms. Because the number of B cells in arterial thrombosis is negligible and B cell-deficiency leads to neutrophilia, we hypothesize that the enhanced arterial thrombosis in B cell-deficient mice is mediated indirectly by neutrophils. Potential neutrophil-mediated mechanisms will tested in vivo by (i) neutrophil depletion, (ii) inhibition of neutrophil cathepsin G and (iii) by preventing neutrophil extracellular trap (NET) formation. The present study on the role and the mechanisms of B cells in arterial thrombosis may provide the first information for future development of novel antithrombotic therapies with less bleeding risk by interfering with B cell- and/or neutrophil-based mechanisms.

• DFG Programme: Research Grants