Outcome of caspase-8 activation in human naïve B cells by optogenetic tools

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PD Dr. Marta Rizzi (CIBSS-AI), Department of Rheumatology and Clinical Immunology
Medical Center, Faculty of Medicine

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Prof. Dr. Bodo Grimbacher (CIBSS-AI), Center for Chronic Immunodeficiency, University Medical Center, Faculty of Medicine

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In B cells the role of caspase-8 has not been thoroughly studied. In CD40 activated naïve B cells, short term (4 hours) FAS engagement results in modulation of the mTOR signaling, changes in transcription (Staniek et al. in revision) and in changes in plasma cell development (preliminary data). We hypothesize that the amount of active caspase-8 and/or duration of caspase-8 activation is an important molecular switch for the integration of signaling between BCR/CD40 activation and FAS or TRAIL-R signaling. In this project, we will use an optogenetic tool with light-induced caspase-8 activity to study the effect of the amount and time of caspase-8 activation on B cell activation, apoptosis, and fate decision. Changes in methylation and chromatin accessibility accompany those cell fate decisions and we will quantify them (Camacho-Ordonez et al., submitted).