Regulation of Autophagy and Apoptosis in B lymphocytes

点击翻译按钮获取中文摘要

The central objective of this proposal is the in-depth analysis of autophagic and apoptotic pathways in B lymphocytes downstream of the B cell antigen receptor (BCR) and CD20. Autophagy is a cellular degradation process which occurs constitutively at basal levels and which appears to fulfil specific functions in B lymphocytes. In turn, the clonal deletion of B lymphocytes with non- or autoreactive antigen receptors plays an important role during B cell development. It has been shown that both processes can be induced by crosslinking the B cell antigen receptor. However, BCR-proximal events remain largely unknown for both cell fate pathways. Next to the analysis of BCR-dependent signal transduction pathways, we will investigate the signalling downstream of the B cell-specific surface molecule CD20, which is the target of monoclonal antibodies used for the treatment of B cell-derived neoplasias and antibody-mediated autoimmune diseases. In addition to the analysis of specific signalling pathways, we also want to characterise the spatial and temporal dynamics of these cell fate decisions downstream of the BCR and CD20. The resulting findings should collectively lead to a better understanding of the mechanisms that regulate B cell homeostasis and that lead to the establishment of central tolerance. Ultimately, we hope to optimise current therapies of B cell-associated diseases by the targeted modulation of autophagic pathways.