Regulation of antigen specific B and CD4 T cell responses
In the department of Immunopathology we investigate how B cell differentiation into IgG-secreting plasma cells (PC) is regulated by antigen and specific signals from follicular Thelper cells. IgG secreting B cells are essential for immunity against pathogens, but also lead to pathology when formed against self-antigens or allo-determinants upon blood transfusion. We investigate how the three signals for IgG B cell differentiation (BCR signalling, CD40 costimulation and T cell-derived cytokines) regulate antigen-specific IgG formation and PC formation. We were the first to demonstrate that recognition of particulate antigen or bacteria by the BCR leads to phagocytosis and optimized T cell-mediated IgG formation. Recently we established a robust system for naïve B cell differentiation into IgG-secreting PC. Using scRNAseq we identified the first linear Bn->PC differentiation pathway known so far and novel cell surface differentiation markers. Besides we established CRISPR-Cas9 technology in primary human B cells to unravel the role of newly identified transcription factors of B->PC differentiation. We use big data analyses and systems biology to unravel immune regulatory networks. In collaboration with the clinics, we study the consequences and relevance of our findings in disease and during treatment.