Uncharted territories Exploring the role of platelets, pO₂ and atypical B cells in the regulation of immune balance

The adaptive immune system is a crucial part of the body’s defense against pathogens and other foreign substances. Throughout this thesis, multiple mechanisms regulating adaptive immune responses are examined. Platelet transfusions are often used to treat patients with low platelet counts or bleeding disorders. However, the transfusion of platelets can also cause adverse immune reactions, such as transfusion-associated immune modulation and the formation of alloantibodies. The first part of this thesis describes immune modulation in the context of platelet transfusions as well as effects of differently glycosylated alloantibodies on platelet clearance upon transfusion. Insights provided in these chapters may help to improve safety and efficacy of platelet transfusions. In the second part of the thesis, the regulation of the dynamics of B cell responses are studied in more detail by investigating how local oxygen levels affect B cell differentiation into antibody-secreting cells (ASCs) and evaluating antigen- specific induction and ASC differentiation capacity of distinct subsets of CD11c⁺ Tbet⁺ B cells. Overall, the research described in this thesis expands our understanding of the mechanisms regulating adaptive immune responses, providing new insights into the dynamics of antibody formation and the factors that influence immune reactions by and to transfused platelets. This knowledge may ultimately be used to develop more effective and safer therapies for a wide range of immune-related disorders.