Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.226662v1?rss=1 Authors: Yam-Puc, J. C., Zhang, L., Maqueda-Alfaro, R. A., Garcia-Ibanez, L., Zhang, Y., Davies, J., Senis, Y. A., Snaith, M., Toellner, K.-M. Abstract: It is still not clear how B-cell receptor (BCR) signalling intensity affects plasma cell and germinal centre (GC) B cell differentiation. We generated Cg1Cre/+Ptpn6fl/fl mice where SHP-1, a negative regulator of BCR signalling, is deleted rapidly after B cell activation. Although immunisation with T-dependent antigens increased BCR signalling, it led to plasma cells reduction and increased apoptosis. Dependent on the antigen, the early GC B cell response was equally reduced and apoptosis increased. At the same time, a higher proportion of GC B cells expressed cMYC, indicating increased GC B cell - Tfh cell interactions. While GC B cell numbers returned to normal at later stages, affinity maturation was suppressed in the long term. This confirms that BCR signalling not only directs affinity dependent B cell selection but also, without adequate Tfh cell help, can inflict cell death, which may be important for the maintenance of B cell tolerance. Copy rights belong to original authors. Visit the link for more info