Prof. Dr. Michael Reth (CIBSS-AI), Institute of Biology III – Molecular Immunology (Faculty of Biology), University of Freiburg
The formation of memory B cells plays a central role for the success of any vaccination program relying on secondary and booster immunizations. Thus, memory B cell function is critical for the control of the pandemic SARS-CoV-2 virus. However, little is known about the maintenance and activation of human memory B cells and the signalling function of the different classes of the B cell antigen receptors (BCRs). In the first CIBSS funding period we studied the nanoscale membrane environment and function of the IgD-class and IgM-class BCR that are co-expressed on naïve mature B cell with major new findings on the cellular location and integrated signaling function of these receptors. Specifically, by combining two revolutionary techniques, namely the lattice light-sheet microscopy (LLSM) and the machine learning image analysis we could describe for the first time the 3-dimensional (3-D) topography of antigen sensing by IgM-class B cells across several biological scales. For these studies we are using the human Burkitt lymphoma cell line Ramos that we developed into a discovery tool for human B cell biology. We have data of the transcriptome, proteome, surfaceome and metabolome of these cells and their off-springs and use the CRISPR/Cas9 technique for human B cell engineering. In the second CIBSS funding period we will develop and apply several control-of-function method to generate memory Ramos B cells and study the nanoscale organisation of their IgG-, IgA- and IgE-class BCRs as well as the integration of normal and oncogenic signalling pathways in human B cells.